摘要
目的探讨硒-甲基硒代半胱氨酸(Se-methyl selenocysteine,MSC)抑制原发性肝癌大鼠肿瘤血管生成的作用及机制。方法选取重庆医科大学实验动物中心提供的清洁级SD大鼠120只,采用随机数字表法分成4组,分别为对照组(30只)、MSC低剂量组(30只)、MSC中剂量组(30只)和MSC高剂量组(30)只,采用小剂量间断DNE法制备原发性肝癌大鼠模型,MSC低、中、高剂量组大鼠分别使用12.5 mmol/L、50 mmol/L和200 mmol/L MSC灌胃,给药剂量为5 ml/kg,对照组使用等剂量生理盐水灌胃,每周5次,共进行6周。采用全自动生化分析仪检测血清AST和ALT水平,酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)法检测血清血管内皮生长因子(vascular endothelial growth factor,VEGF)、低氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)水平,观察大鼠肝脏病理状态,采用免疫组织化学法检测大鼠微血管密度(microvascular density,MVD)与组织内VEGF、HIF-α的表达。结果 MSC低剂量组AST水平最高,对照组ALT水平最高,组间大鼠血清AST、ALT水平差异有统计学意义(F值分别为13.057、12.991,P值分别为0.015,0.023)。对照组大鼠HIF-1α、VEGF及MVD水平最高,组间差异有统计学意义(F值分别为13.054、12.973、13.068,P值分别为0.029、0.014、0.032)。MSC中、高剂量组大鼠肝组织内VEGF、HIF-1α表达强度显著低于对照组(χ~2值分别为13.521、14.205,P值分别为0.042、0.033)。结论 MSC可有效抑制原发性肝癌大鼠模型瘤体中新生血管的生成,其机制与MSC抑制癌组织内HIF-1α和VEGF的表达有关。
Objective To investigate the inhibitory effects and mechanisms of selenium-methylselenocysteine(MSC)on angiogenesis of rats with primary liver cancer.Methods Total of 120 clean SD rats were selected from Experimental Animal Center of Chongqing Medical University and divided into control group(30 rats),MSC low-dose group(30 rats),MSC medium-dose group(30 rats)and MSC high-dose group(30 rats)according to the random number table method.The rat model of hepatocellular carcinoma was established by low-dose intermittent DNE method.Rats in low,middle and high doses group of MSC were administrated with 12.5 mmol/L,50 mmol/L and 200 mmol/L,the dosage was 5 ml/kg.The rats in the control group were given equal dosage of normal saline,5 times a week for 6 weeks.The levels of serum AST and ALT were detected by automatic biochemical analyzer and the serum levels of VEGF and HIF-1αwere detected by enzyme-linked immunosorbent assay(ELISA).The pathological changes of liver tissues were observed.The expression of VEGF and HIF-αin MVD and the tissues were detected by immunohistochemistry.Results The serum levels of AST in the low-dose MSC group was the highest and the serum levels of ALT in the control group was the highest.There were statistically significant differences in serum AST and ALT levels among the four groups(F=13.057,12.991;P=0.015,0.023).The levels of HIF-1α,VEGF,and MVD of rats in control group were the highest and had statistically significant differences among the four groups(F=13.054,12.973,13.068;P=0.029,0.014,0.032).The expression of VEGF and HIF-1αin liver tissue of middle and high dose groups of MSCs were significantly lower than those of the control group(χ2=13.521,14.205;P=0.042,0.033).Conclusion MSC can effectively inhibit the neovascularization in rats with primary liver cancer,and the mechanism may be related to the inhibition of HIF-1αand VEGF expression in primary liver cancer by MSC.
作者
邓银芝
丁俊
张家耀
张勇
李锦貌
樊斌
DENG Yin-zhi;DING Jun;ZHANG Jia-yao;ZHANG Yong;LI Jin-mao;FAN Bin(Department of Gastroenterology,The Central Hospital of Enshi Autonomous Prefecture,Enshi 445000,Hubei Province,China;Department of Hepatobiliary Surgery,The Central Hospital of Enshi Autonomous Prefecture,Enshi 445000,Hubei Province,China)
出处
《中国肝脏病杂志（电子版）》
CAS
2018年第2期82-86,共5页
Chinese Journal of Liver Diseases：Electronic Version
基金
恩施土家族苗族自治州科技计划项目(E20170006)
关键词
肝癌
原发性
硒-甲基硒代半胱氨酸
新生血管
大鼠
Liver cancer,primary
Selenium-methylseleno-cysteine
Neovascularization
Rats
