【作者】 李大可；

【导师】 尹常健；

【作者基本信息】 山东中医药大学 ， 中西医结合临床， 2008， 博士

【摘要】 目的:探讨解毒饮防治雷公藤所致急性药物性肝损害的作用机制。方法:实验一以昆明系小鼠50只,除10只作为正常对照组外,余40只以不同剂量雷公藤多苷灌胃,建立急性药物性肝损害模型,摸索适合造模的雷公藤剂量。实验二以90只小鼠随机分为6组,除空白对照组和模型对照组外,其余各组给予解毒饮低、中、高剂量相应剂量药物和硫普罗宁分别灌胃治疗。7天后参照实验一摸索出的合适剂量的雷公藤多苷建立药物性肝损害模型。造模24小时后,各组小鼠全部处死,测量小鼠体重、肝湿重,计算肝脏系数;检测各组小鼠血清肝功能指标(ALT、AST)、各组小鼠肝组织匀浆肿瘤坏死因子(TNFα)、丙二醛(MDA)、谷胱甘肽(GSH)、过氧化脂质(LPO)含量以及超氧化物歧化酶(SOD)活性;各组小鼠肝组织行HE染色,Bcl-2、CYP2E1免疫组化染色,阳性结果作定量分析。结果:实验一显示,以雷公藤多苷成人正常用量20倍剂量灌胃的小鼠肝损害明显,且死亡率较低。实验二所测得数据经统计学处理后发现:与空白对照组比较,模型对照组上述各项指标均显示异常(P<0.05,P<0.01);而与模型对照组比较,各用药组均能不同程度地改善上述各指标(P<0.05,P<0.01),其中,中药中剂量组明显优于西药对照组(P<0.05)。结论:解毒饮可有效防治雷公藤多苷引起的急性药物性肝损害,其疗效机制包括:降低脂质过氧化反应,提高抗氧化能力,减少细胞色素P450ⅡE1的活性表达,减轻肝组织炎性细胞浸润,减少细胞因子尤其是TNFα的释放,抑制肝细胞凋亡等,从而减轻肝细胞变性坏死程度,促进肝细胞修复。更多还原

【Abstract】 Objective:To explore the mechanism of Jiedu Decoction for preventing and treating Acute Drug-induced Liver Damage(DILD) caused by Tripterygium Glycosides(TG).Methods:In the first experiment, to explore the dosage of TG for building the proper model of acute DILD, 50 normal KD mice were divided into 5 groups, and different doses of TG tablets were given to 4 groups respectively, leave l group as normal samples. The dosage of TG for the proper model of acute DILD is recorded.In the second experiment, 90 new mice were divided into 6 groups in average: one as normal group, one as model group, one was given Tiopronin, and the others were given low, middle and high dose of Jiedu Decoction respectively. 7 days later, all the groups, except the normal one, were given TG tablets according to the dosage recorded in the first step. 24 hours later, all the mice were anatomized for observing. The effects of Jiedu decoction on ALT, AST, TNFα, MDA, SOD, GSH , LPO, Bcl-2 and CYP2E1 were recorded and analyzed.Results:In the first experiment, the acute liver damage of the mice with 20 times dosage of TG for adult is obvious, and the death rate of them is low. So, 20 times of TG for adult is the proper dosage for building the model of acute DILD. In the second experiment, compared with the normal group, all the above indexes for model group are abnormal (P<0.05); however, the indexes for all the mice in the treated groups are improved than the ones for the model group; and the indexes for the group with middle dose of Jiedu Decoction are improved obviously (P<0.05).Conclusion:Jiedu Decoction is an effective drug to prevent and treat acute DILD, which mechanisms includes: lessening the degeneration and promoting the cytothesis of hepatic cells, elevating the antioxygen ability of hepatic cells, decreasing the active expression of CYP2E1, lessening inflammatory cell to infiltrate, reducing the release of cytokine especial TNFαand suppressing apoptosis of hepatic cell.更多还原