解毒饮防治雷公藤所致药物性肝损害作用机制的实验探究.pdf

提 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（P0.05 ，P0.01 ）；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（P0.05 ，P0.01 ），其中，中药中剂量组明显 优于西药对照组（P0.05 ）。 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P450 ⅡE1 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。 关键词 解毒饮；急性药物性肝损害；雷公藤；实验研究 Research on the Mechanism of Jiedu Decoction for Preventing and Treating Acute Drug-induced Liver Damage Caused by Tripterygi Glycosides Speciality: Clinical Study of Integrated TCM and Western Medicine Author: Li Dake Tutor: Professor Yin Changjian 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 norm