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兔体内鸢尾苷元血药浓度与给药剂量和降脂疗效的相关性

Correlation of Blood Concentration and Drug Dose and Reducing Lipid Efficacy of Tectorigenin in Rabbits
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摘要 目的探讨鸢尾苷元(tectorigenin)在动脉粥样硬化(AS)模型兔体内的血药浓度与给药剂量和降脂疗效的相关性。方法48只健康雄性日本大耳白兔随机分为6组。正常对照组给予普通饲料、模型组及各给药组均给予高脂饲料喂养。鸢尾苷元高、中、低剂量组分别给予鸢尾苷元50、25、12.5 mg·kg^(-1)·d^(-1),阳性对照组给予阿托伐他汀5 mg·kg^(-1)·d^(-1)。给药第8周采血,高效液相色谱法检测鸢尾苷元血药浓度。连续给药12周,全自动生化分析仪检测血脂;分离胸腹主动脉段,大体观察血管内膜斑块形成情况;剪取主动脉弓下缘血管段行病理检查。结果鸢尾苷元的平均稳态血药浓度随着给药剂量的增加而增加,具有显著的相关性(r=0.969 1),但并非等比例增加。鸢尾苷元高、中、低剂量组均可显著降低AS模型兔血清总胆固醇、低密度脂蛋白胆固醇和甘油三酯水平,并升高高密度脂蛋白胆固醇,抑制血管内膜增生,但作用强度不如阿托伐他汀组。结论鸢尾苷元在AS模型兔体内的血药浓度与给药剂量相关,具有明显降脂和抗AS作用。 OBJECTIVE To investigate the correlation of blood concentration and drug dose and reducing lipid efficacy of tectorigenin in atherosclerosis rabbits. METHODS Forty-eight Japanese white rabbits were randomly divided into six groups, the normal control group, model group, high-, middle-and low-dose (50, 25, 12.5 mg·kg-1·d-1) tectorigenin groups and atorvastatin (5 mg·kg-1·d-1) group. The normal control group was fed with routine forage, and the other groups were fed with high fat forage for the establishment of atherosclerosis model. After 8 weeks, tectorigenin blood concentration was detected by HPLC. After 12 weeks, blood lipids were detected with automatic biochemical analyzer. We sheared the thoracic and abdominal aorta to observe the formation of atherosclerotic plaque and make pathologic examination. RESULTS Steady-state blood concentration increased with the increase of drug dose, there was a positive relationship (r=0.969 1) between them, but not the same proportion. After treatment, serum total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol (LDL-C ) levels were decreased and high density lipoprotein cholesterol (HDL-C) were increased in the tectorigenin each dose group, but the effect was weaker than atorvastatin group. CONCLUSION Tectorigenin has obvious effect on reducing blood lipid and anti-atherosclerosis in rabbits, and it is related to the blood concentration and the drug dose.
作者 王金凤 王国玉 杨翠燕 王芳 房毅 刘博婧 WANG Jin-feng WANG Guo-yu YANG Cui-yan WANG Fang FANG Yi LIU Bo-jing(The th . 208 Hospttal of Chinese People Liberation Army, Changchun 130062, China)
出处 《中国药学杂志》 CAS CSCD 北大核心 2017年第2期119-123,共5页 Chinese Pharmaceutical Journal
基金 吉林省科技发展计划项目(20140204040YY)
关键词 鸢尾苷元 稳态血药浓度 血脂 动脉粥样硬化 tectorigenin steady-state concentration blood lipid atherosclerosis
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