何首乌对于肾虚模型大鼠肝毒性机制的实验研究

Study on the Mechanism of Liver Toxicity Induced by Polygoni Multiflori Radix(PMR) and Polygoni Multiflori Praeparata Radix Decoction in Rats

目的:探讨何首乌致大鼠肝脏损害的毒性机制。方法:SD大鼠分成两组分别造肾阳虚、肾阴虚模型,两模型组大鼠随机分为制首乌高剂量组(24 g/kg)、中剂量组(12 g/kg)、低剂量组(6 g/kg)、生首乌组(12 g/kg)和正常组,连续灌胃给药或蒸馏水3个月后,腹主动脉取血,离心,取血清检测AST(谷草转氨酶)、ALT(谷丙转氨酶)、ALP(碱性磷酸酶)、TBIL(总胆红素)、IBIL(间接胆红素)。取肝脏观察肝细胞形态学改变。采用ELISA法测定肝组织中炎症介质肿瘤坏死因子TNF-α水平。检测肝线粒体Na^+K^+-ATP酶、Ca^(2+)Mg^(2+)-ATP酶活性。结果:肾阳虚模型大鼠血清5个生化指标有不同程度的变化,而肾阴虚组除生首乌灌胃的大鼠之外未见显著改变。炎症介质TNF-α含量明显升高。Na^+K^+-ATPase、Ca^(2+)Mg^(2+)-ATPase水平下降。结论:生首乌对大鼠有肝毒性,制首乌对肾阳虚模型有一定的肝损伤,何首乌致大鼠肝毒性的机制可能与炎症因子的增加导致线粒体功能障碍有关。

Objective： To explore the mechanism of the liver injury caused by giving Polygoni Multiflori Radix（PMR） and its traditional processed products decoction in rats. Methods： The SD rats were divided into two groups which were made Kidney-Yang Deficiency Model and Kidney-Yin Deficiency Model, the two groups rats then were randomly divided into four groups： normal group, processed products group（high, middle, low dose）, PMR group which were administrated respectively with distilled water or equal volume of PMR and its traditional processed products decoction daily by gavage for consecutive 3 months. The blood of the animals was collected by abdominal aorta. The activities of serum alanine aminotransferase（ALT）, aspartate aminotransferase（AST）, alkaline phosphatase（ALP）, total bilirubin（TBIL） and indirect bilirubin（IBIL） were determined by automatic biochemical analyzer. The livers were collected. Liver pathological changes were observed.The contents of tumor necrosis factor-α（TNF-α） in liver samples were detected by ELISA. Na~＋K~＋-ATPase, Ca^（2＋）Mg^（2＋）-ATPase of hepatic mitochondria were detected. Results： Five biochemical indexes from rats serum of Kidney-Yang Deficiency model had significant changes in different degree. There was no significant change in rats of Kidney-Yin Deficiency group except PMR group. The content of TNF-αof liver significantly increased. The vitality of Na~＋K~＋-ATPase, Ca^（2＋）Mg^（2＋）-ATPase decreased. Conclusions： Liver injury was caused by PMR and its traditional processed products decoction of Kidney-Yang Deficiency Model. The mechanism of the liver injury caused by PMR and its traditional processed products decoction in rats may be related to inflammatory response and energy metabolism.