维拉帕米和尼群地平对大鼠肝硬化作用的实验研究

Effect of verapanil plus nitrendipine on liver cirrhosis in rats

目的 观察维拉帕米和尼群地平对大鼠肝硬化模型的治疗效果 ,并探讨其作用机制 ,以寻求用钙拮抗剂治疗肝病的新途径。方法 80只Wistar大鼠分为正常对照组、肝硬化模型组、维拉帕米组、尼群地平组、联合用药组。第 4周、第 8周测血清谷丙转氨酶 (ALT)、总胆红素 (TBIL)、透明质酸 (HA)、Ⅳ型胶原 (Ⅳ -C) ,肝组织切片分析。结果 维拉帕米和尼群地平有降低ALT和TBIL的作用 ,对肝硬化的指标HA和Ⅳ -C也有改善 ,且联合用药效果更佳。病理证明两种药物能减轻肝细胞变性坏死程度 ,延缓假小叶形成。结论 维拉帕米和尼群地平联合使用 ,可以有效地预防CCl4/乙醇对大鼠肝功能的损伤 ,降低肝硬化程度。

Objective To observe the effect of verapanil plus nitrendipine on the chronic liver cirrhosis of rats induced by CCl 4,so as to find a new way to treat the liver disease by using calcium channel blockers. Methods Eighty Wistar rats were divided into normal control group ,liver cirrhosis model group, verapanil group, nitrendipine group and double-drug group. At the fourth and eighth week, the parameters of serum ALT, TBIL, hyaluronic acid(HA) and type Ⅳ collagen(Ⅳ-C) were measured and historical staining of hepatic tissue was evaluated. Results Verapanil and nitrendipine decreased the level of ALT, TBIL, HA and Ⅳ-C, and both drugs had a better effect in double-drug group. In histopathology, two drugs could reduce the hepatocell degeneration and necrosis and delay the formation of pseudo-lobe. Conclusion Verapanil plus nitrendipine can protect liver function in rats with CCl 4/ethanol-induced fibrosis and significantly decrease the extent of hepatic fibrosis.