柴芍六君子汤拮抗莪术致大鼠肝细胞线粒体损伤的研究

Studies of Chaishao Liujunzi Decoction against hepatic mitochondrial damage in rats caused by Rhizoma Zedoariae

目的比较莪术及莪术配伍柴芍六君子汤后治疗大鼠肝硬化的疗效和副作用。方法运用牛血清白蛋白(BSA)致大鼠免疫性肝硬化模型,应用不同剂量和不同疗程的莪术和莪术+柴芍六君子汤治疗,分别在用药20和40d时处死大鼠,运用超速离心法分离线粒体,检测肝细胞线粒体还原性谷胱甘肽(GSH)、Na+-K+-ATP酶、Ca2+-ATP酶、Ca2+含量。结果莪术能够促使肝细胞线粒体的钙超载,降低其ATP酶的活性,大剂量的莪术能够诱导线粒体内的脂质过氧化反应,增加脂质过氧化产物。同时,莪术还可以降低Bcl-2在肝细胞上的表达量;柴芍六君子汤可以在一定程度上拮抗莪术对肝细胞线粒体的损伤(以ATP酶升高及钙离子下降最为明显)及升高Bcl-2在肝细胞上的表达量。结论肝硬化时大剂量莪术可加重肝细胞损伤,莪术配合柴芍六君子汤可以降低其对肝细胞的损伤。

[Objective] To investigate the effects and side effects of Rhizoma Zedoariae or Rhizoma Zedoariae in combination with Chaishao Liujunzi Decoction in the treatment of cirrhosis of liver in rats. [Methods] The models of cirrhosis of liver in rats were established by injection with bovine serum albumin（BSA）. The rats were treated with Rhizoma Zedoariae or Rhizoma Zedoariae in combination with Chaishao Liujunzi Decoction with different dosage and courses of treatment, and the rats were put to death 20 and 40 days respectively after the medication. The mitochondria were separated with ultracentrifugation and the contents of reduced glutathione （GSH）, Na^＋-K^＋-ATPase, Ca^2＋- ATPase and Ca^2＋ in mitochondria were detected. [Results] With the treatment of Rhizoma Zedoariae, the hepatic mitochondrial calcium overload was found and the activity of ATPase was decreased. Large dosage of Rhizoma Zedoariae induced the intramitochondfial lipid peroxidation and increased the products of lipid peroxidation. The expression of Bcl-2 was decreased in hepatoeyte with the treatment of Rhizoma Zedoariae. With the treatment of Chaishao Liujunzi Decoction, the hepatic mitochondrial damage caused by Rhizoma Zedoariae was decreased in curtain degree, and the expression of Bcl-2 in hepatocyte was increased. [Conclusion] In patients with cirrhosis of liver, the hepatic mitochondrial damage can be enhanced with the treatment of large dosage of Rhizoma Zedoariae, and the damage can be decreased with the treatment of Rhizoma Zedoariae in combination with Chaishao Liujunzi Decoction.