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IMMUNOCHEMICAL IDENTIFICATION AND LOCALIZATION OF CYTOCHROME P-450HSjISOZYME, AN ENZYME RELATED TO NITROSAMINE METABOLISM, IN HUMAN GASTRIC MUCOSA AND GASTRIC CARCINOMA
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作者 方策 沈云英 +1 位作者 吴德丰 潘秀森 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1989年第2期19-23,共5页
Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistoc... Monoclonal antibody (MAb) to rat liver cyto-chrome P-450j isozyme, an activating enzyme specific to nitrosamine metabolism, was used coupled with immunoblotting, densitometer scanning of SDS-PAGE gels and immunohistochemical technique. The trace P-450HSj isozyme (Mr. 51.5 Kd) was found in human gastric mucosa. It was similar to P-450j in molecular weight, catalytic and immunochemical properties. The concentrations of P-450HSj in mucosa of lesser curvature were higher than those in greater curvature. This might be one of the important reasons that lesser curvature is the commonest area for gastric carcinoma. But there was possibly less P-450HSj in gastric mucosa with cancer. Im-munohistochemically, P-450HSj was discovered in the cytoplasm of some glandular epithelial cells, especially in the glands with hyperplastic and intestinal metaplastic changes adjacent to carcinoma. It was also found in some normal glands and in tumor cells of high-differentiated adenocarcinoma, but not in those of low-differentiated ones. Following subjects are discussed: (1) the method of detecting trace P-450HSj, (2) the rule of distribution of P-450HSj, and (3) the relationship between the isozyme and the occurrence of gastric cancer caused by nitrosa-mines. 展开更多
关键词 IN HUMAN GASTRIC MUCOSA AND GASTRIC CARCINOMA AN enzyme RELATED TO NITROSAMINE METABOLISM IMMUNOCHEMICAL IDENTIFICATION AND LOCALIZATION OF cytochrome p-450HSjISOZYME NDEA
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Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle,Fujian Province 被引量:26
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作者 Lin Cai~1 Shun-Zhang Yu~2 Zuo-Feng Zhang~3 1 Department of Epidemiology,Fujian Medical University,Fuzhou 350004,Fujian Province,China2 Department of Epidemiology,Shanghai Medical University,Shanghai 200032,China3 Department of Epidemiology,UCLA School of Public Health,Los Angeles California,USA 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第6期792-795,共4页
AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic... AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in the development of gastric cancer in Changle county, Fujian Province. 展开更多
关键词 Polymorphism genetic Aged Asian Continental Ancestry Group Case-Control Studies China cytochrome p-450 CYP2E1 Female Gene Frequency genetic Predisposition to Disease Humans Male Middle Aged Research Support Non-U.S. Gov't Stomach Neoplasms
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Effects of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on cytochrome P450 enzyme activities in rats 被引量:3
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作者 LIU Xin WANG Xinyu +1 位作者 PENG Yinxuan WANG Xing 《Journal of Traditional Chinese Medicine》 SCIE CSCD 2021年第2期284-292,共9页
OBJECTIVE:To investigate the efficacy of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on cytochrome P450(CYP450)enzyme activities in rats.METHODS:A cocktail strategy was followed to ... OBJECTIVE:To investigate the efficacy of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on cytochrome P450(CYP450)enzyme activities in rats.METHODS:A cocktail strategy was followed to evaluate the influence of Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)on the activities of CYP450 isoforms(CYP1A2,CYP3A4,CYP2E1,CYP2C19,CYP2C9,CYP2D6),which were determined by changes in the pharmacokinetic parameters of six probe drugs,theophylline,dapsone,chlorzoxazone,omeprazole,tolbutamide and dextromethorphan.Study groups included,Control group(CG),Tianma(Rhizoma Gastrodiae)group(TM),Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)group(GT)and Tianma Gouteng(Gastrodia Uncaria)group(TMGT).RESULTS:No significant differences between Tianma(Rhizoma Gastrodiae)and control groups were found.Compared with the control group,in the Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis)group both the AUC and t1/2 of dapsone and tolbutamide were reduced,whereas the CL(clearance rate)of dapsone and tolbutamide were increased.Compared with the control group,in the Tianma Gouteng group,the AUC and t1/2 of dapsone and tolbutamide were reduced,the CL of dapsone and tolbutamide were increased,and the AUC and t1/2 of chlorzoxazone were increased and the CL of chlorzoxazone was reduced.CONCLUSION:Tianma(Rhizoma Gastrodiae)has no significant effect on the six CYP450 subtypes.The activities of CYP3A4 and CYP2C9 were increased by Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis).The activities of CYP3A4 and CYP2C9 were increased,whereas the activity of CYP32E1 was reduced by combined Tianma(Rhizoma Gastrodiae)and Gouteng(Ramulus Uncariae Rhynchophyllae cum Uncis). 展开更多
关键词 Gastrodiae Elata Ramulus Uncariae Cum Uncis cytochrome p-450 enzyme system cocktail probe drug
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Immunohistochemical localization of cytochrome P450 enzymes 2C and 4A in the normal rat brain
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作者 黄存斌 《Chinese Medical Journal》 SCIE CAS CSCD 1998年第11期48-53,共6页
Objective To localize cytochrome P450 enzymes 4A and 2C in central nervous cells of normal male rats.Methods Eight drug/alcohol untreated normal male rats (150-200 g of body weight) were treated by the optimized perfu... Objective To localize cytochrome P450 enzymes 4A and 2C in central nervous cells of normal male rats.Methods Eight drug/alcohol untreated normal male rats (150-200 g of body weight) were treated by the optimized perfusion technique, then brain tissues were postfixed, paraffin-embedded and cut into series sections, which were labeled by the improved strept-avidin-biotin complex DAB-nickel enhancer (SABC-DAB-Ni) immunohistochemistry and hematoxylin & eosin (H & E) stain techniques.Results The immunohistochemical results indicated that P450 2C-11 enzyme was localized in diverse numbers of neurons as well as some neuroglial cells, with focal or defuse distribution in many brain regions such as cerebrum, thalamus, olfactory bulb, hypothalamus, brain-stem, hippocampus, cerebellum, interpositus nucleus, caudate-putamen, and globus pallidus. In contrast, no positive findings of P450 4A-2, 3 and 8 enzymes were obtained in the same animals. With high magnification, 2C-11 protein was able to be roughly observed on the endoplasmic reticulum of the rat neurons.Conclusions P450 2C-11 protein, rather than P450 4A-2, 3 and 8, may be a candidate of brain P450 enzymes in the normal male rats. 展开更多
关键词 Aryl Hydrocarbon Hydroxylases Steroid 16-alpha-Hydroxylase Animals BRAIN cytochrome p-450 enzyme System Immunohistochemistry Male RATS Rats Sprague-Dawley Steroid Hydroxylases
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细胞色素P450 2C19基因多态性与原发性肝细胞癌的相关性研究 被引量:5
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作者 蒋文 邵建国 陆建荣 《胃肠病学》 2008年第1期39-41,共3页
背景:细胞色素P450(CYP)2C19代谢美芬妥英的酶活性在人群中呈快代谢型和慢代谢型二态分布。突变型等位基因是CYP2C19基因多态性的分子生物学基础。目的:对原发性肝细胞癌(HCC)患者的CYP2C19等位基因进行基因分型,探讨CYP2C19基因多态性... 背景:细胞色素P450(CYP)2C19代谢美芬妥英的酶活性在人群中呈快代谢型和慢代谢型二态分布。突变型等位基因是CYP2C19基因多态性的分子生物学基础。目的:对原发性肝细胞癌(HCC)患者的CYP2C19等位基因进行基因分型,探讨CYP2C19基因多态性与原发性HCC的关系。方法:纳入48例原发性HCC患者和88名健康对照者。设计相应引物,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测CYP2C19m1和CYP2C19m2突变型等位基因,对两组基因多态性进行分析比较。结果:HCC组CYP2C19慢代谢型(m1/m1和m1/m2)发生率为25.0%(12例),与健康对照组的11.4%(10例)相比差异有统计学意义(P<0.05,OR=3116,95%CI:1140~7113)。结论:CYP2C19慢代谢型与原发性HCC之间存在相关性,可能增加人群对HCC的易感性。 展开更多
关键词 肝肿瘤 细胞色素P450酶系统 多态现象 遗传
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孕烷X受体介导佐米曲坦对大鼠肝细胞色素P450 CYP 3A的诱导作用 被引量:1
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作者 邢峰 余露山 曾苏 《浙江大学学报(医学版)》 CAS CSCD 北大核心 2009年第3期249-254,共6页
目的:考察佐米曲坦对大鼠肝细胞色素P450 CYP3A1/2的诱导是否由孕烷X受体(PXR)介导。方法:在构建的基于PXR的荧光素酶报告基因上,观察不同浓度佐米曲坦(10、50、100μmol.L-1)对大鼠肝细胞色素P450 CYP3A1/2的诱导作用。以经典的诱导剂1... 目的:考察佐米曲坦对大鼠肝细胞色素P450 CYP3A1/2的诱导是否由孕烷X受体(PXR)介导。方法:在构建的基于PXR的荧光素酶报告基因上,观察不同浓度佐米曲坦(10、50、100μmol.L-1)对大鼠肝细胞色素P450 CYP3A1/2的诱导作用。以经典的诱导剂16α-氰基孕烯醇酮(PCN)作为阳性对照,空白溶剂(DMSO)作为阴性对照。结果:与阴性对照组相比,阳性对照组、佐米曲坦在100μmol.L-1浓度时,对CYP3A1有明显的诱导作用,活性分别增加了1.93、1.96倍(P<0.05);阳性对照组、佐米曲坦10μmol.L-1、50μmol.L-1浓度组对CYP3A2也有明显的诱导作用,其活性分别增加了2.51、2.10、1.63倍(P<0.01、<0.05)。结论:PXR通路是佐米曲坦诱导大鼠CYP3A1/2的一个重要途径。 展开更多
关键词 细胞色素P450酶系统/遗传学 恶唑烷酮类/投药和剂量 恶唑烷酮类/分析 受体 胞质和核/代谢
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GSTT1,GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population 被引量:11
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作者 Jucimara Colombo Ana Elizabete Silva +3 位作者 Andréa Regina Baptista Rossit Alaor Caetano Aldenis Albaneze Borim Durval Wohnrath 《World Journal of Gastroenterology》 SCIE CAS CSCD 2004年第9期1240-1245,共6页
AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducte... AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducted a study on 100 cases of gastric cancer (GC),100 cases of chronic gastritis (CG),and 150 controls (C).Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR.CYP2E1/Pst1 genotyping was performed using a PCR-RFLP assay. RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups.However,a significant difference between CG and C was observed,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group.The GSTT1 null genotype occurred more frequently in Negroid subjects,and the GSTM1 null genotype in Caucasians,while the GSTM1 positive genotype was observed mainly in individuals with chronic gastritis infected with H pylori. CONCLUSION:Our findings indicate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer. 展开更多
关键词 Polymorphism genetic Adolescent Adult Aged Aged 80 and over Brazil Case-Control Studies Chronic Disease cytochrome p-450 CYP2E1 Female Gastritis Genotype Glutathione Transferase Humans Male Middle Aged Research Support Non-U.S. Gov't Risk Factors Stomach Neoplasms
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GSTM1,GSTT1,GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population:Different pattern of squamous cell carcinoma and adenocarcinoma 被引量:7
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作者 Ahmed Abbas Karine Delvinquière +4 位作者 Mathilde Lechevrel Pierre Lebailly Pascal Gauduchon Guy Launoy Fran ois Sichel 《World Journal of Gastroenterology》 SCIE CAS CSCD 2004年第23期3389-3393,共5页
AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. ... AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione. 展开更多
关键词 ACYLTRANSFERASES ADENOCARCINOMA Adult Aged Aged 80 and over Carcinoma Squamous Cell Case-Control Studies cytochrome p-450 CYP1A1 Esophageal Neoplasms Female France genetic Predisposition to Disease Genotype Glutathione Transferase Humans Male Middle Aged Polymorphism genetic Research Support Non-U.S. Gov't Risk Factors
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细胞色素P450基因多态性与药物性肝损伤的关系 被引量:7
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作者 王巧玲 邹正升 《临床肝胆病杂志》 CAS 北大核心 2020年第5期1150-1153,共4页
随着药物性肝损伤患病率的逐年上升,药物性肝损伤发病机制成为了关注的焦点。CYP450酶作为一个庞大的家族,参与了药物在人体肝脏内的几乎所有氧化代谢反应。近年来发现CYP450酶的基因多态性导致了药效动力学在不同个体中的代谢差异性,... 随着药物性肝损伤患病率的逐年上升,药物性肝损伤发病机制成为了关注的焦点。CYP450酶作为一个庞大的家族,参与了药物在人体肝脏内的几乎所有氧化代谢反应。近年来发现CYP450酶的基因多态性导致了药效动力学在不同个体中的代谢差异性,故探索CYP450酶基因多态性在药物性肝损伤中的作用,可促进对药物性肝损伤发病机制的了解。对已发现与药物性肝损伤相关的CYP450酶基因多态性进行综述。 展开更多
关键词 细胞色素P450酶系统 多态现象 遗传 化学性与药物性肝损伤
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Interactions of chemical carcinogens and genetic variation in hepatocellular carcinoma 被引量:1
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作者 Yu-Jing Zhang 《World Journal of Hepatology》 CAS 2010年第3期94-102,共9页
In the etiology of hepatocellular carcinoma (HCC), in addition to hepatitis B virus and hepatitis C virus infections, chemical carcinogens also play important roles. For example, aflatoxin B 1 (AFB 1 ) epoxide reacts ... In the etiology of hepatocellular carcinoma (HCC), in addition to hepatitis B virus and hepatitis C virus infections, chemical carcinogens also play important roles. For example, aflatoxin B 1 (AFB 1 ) epoxide reacts with guanine in DNA and can lead to genetic changes. In HCC, the tumor suppressor gene p53 codon 249 mutation is associated with AFB 1 exposure and mutations in the K -ras oncogene are related to vinyl chloride exposure. Numerous genetic alterations accumulate during the process of hepatocarcinogenesis. Chemical carcinogen DNA-adduct formation is the basis for these genetic changes and also a molecular marker which reflects exposure level and biological effects. Metabolism of chemical carcinogens, including their activation and detoxification, also plays a key role in chemical hepatocarcinogenesis. Cytochrome p450 enzymes, N -acetyltransferases and glutathione S -transferases are involved in activating and detoxifying chemical carcinogens. These enzymes are polymorphic and genetic variation influences biological response to chemical carcinogens. This genetic variation has been postulated to influence the variability in risk for HCC observed both within and across populations. Ongoing studies seek to fully understand the mechanisms by which genetic variation in response to chemical carcinogens impacts on HCC risk. 展开更多
关键词 Hepatocellular carcinoma Chemical CARCINOGENS AFLATOXIN B 1 POLYCYCLIC aromatic hydrocarbons 4-aminobiphenyl HEPATITIS B VIRUS HEPATITIS C VIRUS Glutathione S -transferase cytochrome p450 enzymes genetic variation
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调整的抗血小板聚集治疗方案对老年未破裂颅内动脉瘤介入治疗围手术期缺血事件发生的影响分析 被引量:7
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作者 顾大群 汪洋 +4 位作者 张扬 晁迎九 高歌 陈昱 余舰 《中国脑血管病杂志》 CAS CSCD 北大核心 2023年第1期20-26,F0003,共8页
目的 探索应用细胞色素P450 2C19(CYP2C19)基因检测调整抗血小板聚集治疗方案对老年未破裂颅内动脉瘤支架辅助弹簧圈栓塞围手术期缺血事件的影响。方法 回顾性连续纳入2018年1月至2021年12月中国科学技术大学附属第一医院神经外科行介... 目的 探索应用细胞色素P450 2C19(CYP2C19)基因检测调整抗血小板聚集治疗方案对老年未破裂颅内动脉瘤支架辅助弹簧圈栓塞围手术期缺血事件的影响。方法 回顾性连续纳入2018年1月至2021年12月中国科学技术大学附属第一医院神经外科行介入治疗的老年(年龄≥60岁)未破裂颅内动脉瘤住院患者343例,依据中国科学技术大学附属第一医院开始开展CYP2C19基因检测技术的时间(2021年1月),将343例老年未破裂颅内动脉瘤患者分为非基因检测组(2018年1月至2020年12月)和基因检测组(2021年1—12月)。非基因检测组采用常规抗血小板聚集治疗方案(阿司匹林100 mg/次和氯吡格雷75 mg/次,1次/d),基因检测组根据CYP2C19基因检测结果调整抗血小板聚集治疗方案(对于超快代谢型及快代谢型患者,给予阿司匹林肠溶片100 mg/次和氯吡格雷75 mg/次,1次/d;对于中间代谢型及慢代谢型患者,给予阿司匹林肠溶片100 mg/次1次/d和替格瑞洛90 mg/次2次/d),比较两组术中及术后1个月内发生缺血事件的差异,同时对影响缺血事件的相关因素进行单因素分析和多因素Logistic回归分析。结果 343例老年未破裂颅内动脉瘤患者中,非基因检测组181例,基因检测组162例。(1)非基因检测组与基因检测组患者性别、年龄、高血压病、糖尿病、高脂血症、吸烟史、颅内动脉粥样硬化、动脉瘤大小、动脉瘤部位、支架类型、动脉瘤栓塞程度、出血事件的差异均无统计学意义(均P>0.05);基因检测组缺血事件发生率低于非基因检测组,组间差异有统计学意义[4.9%(8/162)比11.6%(21/181),χ^(2)=4.905,P=0.027]。(2)发生缺血事件组与未发生缺血事件组患者性别、年龄、高血压病、糖尿病、高脂血症、动脉瘤大小、动脉瘤部位、动脉瘤栓塞程度的差异均无统计学意义(均P>0.05);未发生缺血事件组患者吸烟、颅内动脉粥样硬化、使用编织型支架比例均低于发生缺血事件组[14.6%(46/314)比31.0%(9/29);17.2%(54/314)比37.9%(11/29),χ^(2)=7.430;24.2%(76/314)比44.8%(13/29),χ^(2)=5.877],使用调整的抗血小板聚集治疗方案比例高于发生缺血事件组[49.0%(154/314)比27.6%(8/29),χ^(2)=4.905],组间差异均有统计学意义(均P<0.05)。(3)发生缺血事件的多因素Logistic回归分析显示,吸烟史(OR=2.845,95%CI:1.177~6.874)、颅内动脉粥样硬化(OR=2.615,95%CI:1.131~6.045)、使用编织支架(OR=2.480,95%CI:1.102~5.584)、使用常规抗血小板聚集治疗方案(OR=2.546,95%CI:1.071~6.051)是老年未破裂颅内动脉瘤介入治疗围手术期发生缺血事件的独立危险因素(均P<0.05)。结论 根据CYP2C19基因检测结果调整的抗血小板聚集治疗方案可以降低老年未破裂颅内动脉瘤患者介入治疗围手术期缺血事件的发生风险。本研究结果仍需大样本数据进一步证实。 展开更多
关键词 基因检测 细胞色素P450酶系统 双重抗血小板治疗 颅内动脉瘤 介入治疗 缺血事件
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CYP1A1多态性与肺癌遗传易感性的关系 被引量:7
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作者 李代蓉 周清华 +4 位作者 郭占林 袁天柱 朱文 王艳萍 陈晓禾 《中华肿瘤防治杂志》 CAS 2006年第23期1765-1768,共4页
目的:探讨代谢酶基因CYP1A1基因多态性与中国汉族人群肺癌遗传易感性之间的相关性。方法:应用AS-PCR技术检测150例中国四川汉族肺癌和152例中国四川汉族健康人的CYP1A1基因Exon 7多态性分布频率,并分析了Exon 7多态性与中国四川汉族... 目的:探讨代谢酶基因CYP1A1基因多态性与中国汉族人群肺癌遗传易感性之间的相关性。方法:应用AS-PCR技术检测150例中国四川汉族肺癌和152例中国四川汉族健康人的CYP1A1基因Exon 7多态性分布频率,并分析了Exon 7多态性与中国四川汉族人群肺癌遗传易感性之间的相关性。结果:CYP1A1 Exon 7 3种多态基因型分布频率在两组间比较差异无统计学意义,X^2=0.634,P=0.728。携带突变Val基因型的个体较携带Ile/Ile基因型的个体患肺癌的危险性增加。OR=1.139,95%CI为0.635~2.042,P=0.662。携带突变Val基因型的个体较携带Ile/Ile基因型的个体患肺鳞癌的风险显著增加,OR=3.510,95%CI=1.326-9.293,P=0.011。结论:Val突变等位基因可能是中国四川汉族人群的肺癌易感基因。CYP1A1基因Exon 7多态性在肺鳞癌发生中起重要作用。 展开更多
关键词 肺肿瘤 多态现象 遗传 代谢 酶类 基因 细胞色素P450 CYP1A1
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pcDNA3.1(+)-CYP19-GFP真核表达质粒构建 被引量:5
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作者 邵喜英 陈占红 +2 位作者 曹江 方永明 王晓稼 《浙江大学学报(医学版)》 CAS CSCD 北大核心 2011年第2期189-194,共6页
目的:构建pcDNA3.1(+)-CYP19-GFP、pcDNA3.1(+)-CYP19W39R-GFP、pcDNA3.1(+)-CYP19R264C-GFP与pcDNA3.1(+)-CYP19W39R-R264C-GFP真核表达质粒,并观察pcDNA3.1(+)-CYP19-GFP质粒在MCF-7和Bcap-37细胞中的表达。方法:①采用RT-PCR技术扩增... 目的:构建pcDNA3.1(+)-CYP19-GFP、pcDNA3.1(+)-CYP19W39R-GFP、pcDNA3.1(+)-CYP19R264C-GFP与pcDNA3.1(+)-CYP19W39R-R264C-GFP真核表达质粒,并观察pcDNA3.1(+)-CYP19-GFP质粒在MCF-7和Bcap-37细胞中的表达。方法:①采用RT-PCR技术扩增CYP19 cDNA,插入pcDNA3.1(+)载体中,构建pcDNA3.1(+)-CYP19表达质粒;酶切pcDNA3.1(+)-CYP19(304bp BamHⅠ)-GFP和pcDNA3.1(+)-CYP19质粒,构建pcDNA3.1(+)-CYP19-GFP表达质粒;②以pcDNA3.1(+)-CYP19-GFP质粒为模板,采用定点突变技术,构建pcDNA3.1(+)-CYP19W39R-GFP和pcDNA3.1(+)-CYP19R264C-GFP及pcDNA3.1(+)-CYP19W39R-R264C-GFP表达质粒;③pcDNA3.1(+)-CYP19-GFP质粒通过脂质体介导转染MCF-7和Bcap-37细胞,荧光显微镜观察其在细胞中的表达。结果:①酶切鉴定及测序验证pcDNA3.1(+)-CYP19-GFP构建成功;②测序验证pcDNA3.1(+)-CYP19W39R-GFP和pcDNA3.1(+)-CYP19R264C-GFP及pcDNA3.1(+)-CYP19W39R-R264C-GFP构建成功;③在经转染的MCF-7和Bcap-37细胞中观察到较强的绿色荧光。结论:pcDNA3.1(+)-CYP19-GFP、pcDNA3.1(+)-CYP19W39R-GFP和pcDNA3.1(+)-CYP19R264C-GFP及pcDNA3.1(+)-CYP19W39R-R264C-GFP真核表达质粒已成功构建,并证实pcDNA3.1(+)-CYP19-GFP质粒能在MCF-7和Bcap-37细胞中表达,为进一步研究CYP19基因单核苷酸多态性的确切功能奠定基础。 展开更多
关键词 细胞色素P450酶系统/遗传学 质粒 遗传载体 真核细胞 CYP19基因 真核表达质粒 GFP
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经皮冠状动脉介入术术后病人CYP2C19*2、CYP2C19*3和PON1基因多态性与氯吡格雷血药浓度及疗效的相关性分析 被引量:5
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作者 范洁 詹三华 袁孔现 《安徽医药》 CAS 2020年第2期385-389,共5页
目的探讨经皮冠状动脉介入术(PCI)术后病人CYP2C19*2、CYP2C19*3及PON1基因多态性与氯吡格雷血药浓度及疗效的相关性。方法采用定时定量焦磷酸测序技术检测CYP2C19*2、CYP2C19*3及PON1基因型。使用反相高效液相色谱法(RP-HPLC)法,以艾... 目的探讨经皮冠状动脉介入术(PCI)术后病人CYP2C19*2、CYP2C19*3及PON1基因多态性与氯吡格雷血药浓度及疗效的相关性。方法采用定时定量焦磷酸测序技术检测CYP2C19*2、CYP2C19*3及PON1基因型。使用反相高效液相色谱法(RP-HPLC)法,以艾司唑仑为内标,测定氯吡格雷、羧酸氯吡格雷(SR26334)血药浓度。结果共纳入51例PCI术后病人,结果显示CYP2C19快代谢型血药浓度(1.09±0.61)μg/mL与慢代谢型SR26334血药浓度(1.54±0.48)μg/mL之间差异有统计学意义(P=0.038 9),PON1(126C>G)野生型(CC型)病人SR26334血药浓度(1.45±0.63)μg/mL与突变型(CG+GG型)病人SR26334血药浓度(1.09±0.32)μg/mL差异有统计学意义(P=0.0408)。SR26334峰浓度与终点事件相关性分析中可见,正常组病人血药浓度(1.51±0.48)μg/mL VS心血管事件组病人血药浓度(1.06±0.65)μg/mL差异有统计学意义(P=0.0481),CYP2C19基因型与终点事件的发生无明显相关。结论基因检测和血药浓度检测可为ACS病人PCI术后个体化抗血小板治疗方案的制订提供依据,可作为临床药师开展药学服务的切入点之一。 展开更多
关键词 细胞色素P450酶系统 对氧磷 氯吡格雷 血药浓度 色谱法 反相 发光测定法 多态现象 遗传 个体化医学
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CYP1B1基因L432V多态性与散发子宫内膜癌风险关系的研究 被引量:1
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作者 朱壮彦 穆雅琴 +2 位作者 富晓敏 李拴明 赵富玺 《实用肿瘤杂志》 CAS 北大核心 2009年第2期114-117,共4页
目的探讨CYP1B1基因L432V多态性与子宫内膜癌发生危险性的关系。方法用等位基因特异性PCR(AS-PCR)法,对72例子宫内膜癌患者和80例正常女性的CYP1B1 L432V多态位点进行检测,确定出多态性的3种基因型,即野生型C/C、杂合型C/G、突变型G/G... 目的探讨CYP1B1基因L432V多态性与子宫内膜癌发生危险性的关系。方法用等位基因特异性PCR(AS-PCR)法,对72例子宫内膜癌患者和80例正常女性的CYP1B1 L432V多态位点进行检测,确定出多态性的3种基因型,即野生型C/C、杂合型C/G、突变型G/G;免疫组化S-P法进一步研究雌激素受体α(ERα)的表达是否受CYP1B1基因多态性的影响。结果CYP1B1基因L432V多态性C/C、C/G、G/G三种基因型分布频率,子宫内膜患者组分别为47.2%、36.1%和16.7%,对照组分别为68.8%、23.8%和7.5%;子宫内膜癌患者组C、G等位基因频率为65.3%,34.7%,对照组为80.6%,19.4%。CYP1B1 L432V多态性基因型及等位基因型在两组间分布频率的差异有统计学意义(P〈0.05)。基因型C/G与C/C比较,G/G与C/C比较OR值分别为2.214(95%CI 1.067-4.593)倍和3.235(95%CI 1.111-9.425)倍;子宫内膜癌ERα表达检测发现,突变基因型G/G、C/G基因型者ERα阳性表达率高于C/C野生基因型(P〈0.05)。结论CYP1B1 L432V多态位点3种基因型的分布与子宫内膜癌发病风险有一定关联,突变基因型增加了子宫内膜癌的发病风险,且与ER的表达相关。 展开更多
关键词 子宫内膜肿瘤/病理学 子宫内膜肿瘤/遗传学 多态现象 遗传 聚合酶链反应 突变 细胞色素P450酶系统 基因型 免疫组织化学
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CYP2C9及VKORC1基因多态性对心脏瓣膜置换术后华法林个体剂量差异的研究 被引量:2
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作者 彭齐 陈晓英 宋杰 《解放军医药杂志》 CAS 2014年第12期16-20,27,共6页
目的研究湖北地区汉族人细胞色素P450酶2C9(CYP2C9)基因和维生素K环氧化物还原酶复合体1(VKORC1)基因多态性分布特点及其对华法林稳态剂量的影响。方法收集2012年3—8月湖北地区汉族临床使用华法林的患者108例作为华法林组,选择同期健... 目的研究湖北地区汉族人细胞色素P450酶2C9(CYP2C9)基因和维生素K环氧化物还原酶复合体1(VKORC1)基因多态性分布特点及其对华法林稳态剂量的影响。方法收集2012年3—8月湖北地区汉族临床使用华法林的患者108例作为华法林组,选择同期健康受试者85名为对照组。采用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)技术检测CYP2C9和VKORC1基因型,并比较不同基因型华法林稳态剂量。结果两组基因型频率和等位基因频率分布比较差异无统计学意义(P>0.05)。华法林组中CYP2C9基因*1/*3型较*1/*1型华法林稳态剂量小,VKORC1基因AA型较GA型华法林稳态剂量小(P<0.05,P<0.01)。除了检测的3个多态位点,还发现了50多个变异位点。结论在湖北地区汉族人群中,存在CYP2C9和VKORC1基因多态性,且不同基因型患者间华法林稳态剂量存在差异,华法林基因相关变异位点需要进一步证实。 展开更多
关键词 华法林 多态现象 遗传 细胞色素P450酶系统 维生素K环氧化物还原酶复合体1
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CYP2D6基因与药物代谢 被引量:4
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作者 施安国 《中国新药与临床杂志》 CAS CSCD 北大核心 2003年第8期491-494,共4页
细胞色素P 45 0 (CYP)中的CYP2D6酶在抗抑郁药、安定药及某些抗心律失常药的代谢中起重要作用 ,CYP2D6基因位于 2 2号常染色体上为隐性遗传 ,CYP2D6基因呈多态性约有 70余种等位基因变异型 ,也存在特异人群差别 ,因而导致所编码的酶活... 细胞色素P 45 0 (CYP)中的CYP2D6酶在抗抑郁药、安定药及某些抗心律失常药的代谢中起重要作用 ,CYP2D6基因位于 2 2号常染色体上为隐性遗传 ,CYP2D6基因呈多态性约有 70余种等位基因变异型 ,也存在特异人群差别 ,因而导致所编码的酶活性不同 ,这些数据有助于理解药物代谢的个体差异、有助于预测药物之间的相互作用。 展开更多
关键词 细胞色素p-450 CYP2D6基因 药物代谢 基因多态性
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利用细菌/杆状病毒系统在昆虫细胞中表达人CYP2E1 被引量:4
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作者 路珂 曾苏 姚彤炜 《浙江大学学报(医学版)》 CAS CSCD 2008年第2期118-125,共8页
目的:获得人CYP2E1重组酶,并用该重组酶的特征性探针底物对其进行代谢活性研究。方法:以人肝组织RNA为模板,通过RT-PCR得到CYP2E1 cDNA片断,然后与pFastBac质粒连接,得到pFastBac-CYP2E1重组质粒,将其转化E.coli DH 10Bac大肠杆菌,通过... 目的:获得人CYP2E1重组酶,并用该重组酶的特征性探针底物对其进行代谢活性研究。方法:以人肝组织RNA为模板,通过RT-PCR得到CYP2E1 cDNA片断,然后与pFastBac质粒连接,得到pFastBac-CYP2E1重组质粒,将其转化E.coli DH 10Bac大肠杆菌,通过转座作用,获得重组Bacmid-CYP2E1,将其转染草地夜蛾细胞(Sf9)后,产生重组杆状病毒。将该病毒以及分别含有人CYPOR和人CYPb5的病毒共同感染Sf9细胞,收集共表达蛋白,以氯唑沙宗为底物鉴定重组酶的活性。结果:利用细菌/杆状病毒系统得到重组人CYP2E1的表达,其对氯唑沙宗的Km值为(72.4±8.7)μmol.L-1,Vmax值为(2.41±0.10)μmol.min-1.g-1蛋白。结论:利用杆状病毒系统成功表达了有催化活性的人CYP2E1重组酶,其活性与文献报道值相似。 展开更多
关键词 杆状病毒科 细胞色素P450酶系统 蛾/细胞学 大肠杆菌/遗传学 重组 遗传 细胞色素P450 杆状病毒 草地夜蛾细胞 氯唑沙宗
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CYP2C19*2和CYP2C19*17基因多态性与冠状动脉介入治疗后病人氯吡格雷反应性的关联分析 被引量:10
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作者 吴晓峰 《安徽医药》 CAS 2019年第4期679-682,共4页
目的探究CYP2C19*2和CYP2C19*17基因多态性与冠状动脉介入治疗后病人氯吡格雷反应性的关系。方法青海省心脑血管病专科医院于2014年3月至2017年3月期间招募了347例经皮冠状动脉介入的支架植入病人。采集经氯吡格雷(75 mg/d)治疗至少7 d... 目的探究CYP2C19*2和CYP2C19*17基因多态性与冠状动脉介入治疗后病人氯吡格雷反应性的关系。方法青海省心脑血管病专科医院于2014年3月至2017年3月期间招募了347例经皮冠状动脉介入的支架植入病人。采集经氯吡格雷(75 mg/d)治疗至少7 d的病人血液样品,用VerifyNow P2Y_(12)测定法测量血小板活性(PRU)和(%)抑制性。应用聚合酶链式反应检测CYP2C19*2(rs4244285)和CYP2C19*17(rs12248560)基因多态性,比较氯吡格雷应答组和无应答组病人CYP2C19*2(rs4244285)和CYP2C19*17(rs12248560)基因型的分布频率差异以及等位基因频率差异。结果分组时,PRU>208的病人对氯吡格雷治疗无反应;104例(30%)病人为无应答者,243例(70%)病人为应答者。243例氯吡格雷应答组和104例无应答组CYP2C19*2(rs4244285)基因型分布频率野生型GG为80.7%/54.8%,杂合型GA为17.3%/38.5%,突变型AA为2.1%/6.7%,两组比较χ~2=7.04,P<0.001;等位基因频率野生型G为89.3%/74.0%,突变型A为10.7%/26.0%,两组比较χ~2=5.25,P<0.001。CYP2C19*17(rs12248560)基因型分布频率野生型CC为67.9%/75.0%,杂合型CT为30.5%/23.1%,突变型TT为1.6%/1.9%,两组比较χ~2=0.81,P=0.388;等位基因频率野生型C为83.1%/84.1%,突变型T为16.9%/13.1%,两组比较χ~2=0.68,P=0.416。结论 CYP2C19*2多态性与氯吡格雷治疗无反应相关,CYP2C19*17多态性增强了氯吡格雷的抗血小板活性。根据这两种多态性的单倍型,氯吡格雷治疗的病人可以被保护或不受支架血栓形成和缺血事件的威胁。 展开更多
关键词 细胞色素P450酶系统 多态现象 遗传 血管成形术 气囊 冠状动脉 氯吡格雷
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Herb-drug enzyme-mediated interactions and the associated experimental methods: a review
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作者 Li Bo Zhao Baosheng +4 位作者 Liu Yang Tang Mingmin Lǚe Beiran Luo Zhiqiang Zhai Huaqiang 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2016年第3期392-408,共17页
OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental methods.METHODS: Definite herb-drug interactions were obtained by searching Pub Med, other large over... OBJECTIVE: To review the interactions between herbs and widely used drugs and summarize the associated experimental methods.METHODS: Definite herb-drug interactions were obtained by searching Pub Med, other large overseas databases and summarizing new researches from China. We summarize some methods to assess the interaction between herbs and drugs involving microsomal, cell culture and animal experiments, and clinical trials, classifying this method as single ingredient herbs, crude herb extracts, andherbal formulae.RESULTS: Many herbs interact with drugs through a complex cytochrome P450 and/or P-glycoprotein mechanism. Herb-induced enzyme inhibition and/or induction may result in enhanced and / or decreased plasma, tissue, urine and bile drug concentrations, leading to a change in a drug's pharmacokinetic parameters and resulting in the improper treatment of patients and potentially severe side effects. Use of an appropriate method for comprehensively assessing herb-drug interactions can minimize clinical risks. Different methods were used by researchers to assess the pharmacological changes of drugs in vivo and in vitro and the mechanisms of the interactions from microsomal, cell culture and animal experiments, and clinical trials are discussed in this review.CONCLUSION: Co-medication with herbs can result in changes in pharmacological effects of many drugs. This review describes the assessment of single-ingredient herbs, crude herb extracts, and herbal formulae. When choosing a research method to investigate herb-drug interactions, the properties of the drugs and herbs should be considered. 展开更多
关键词 Herb-drug interaction METABOLISM cytochrome p-450 enzyme system p-GLYCOPROTEIN REVIEW
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