复方滋阴颗粒对长期给药大鼠肝肾毒性的影响

Effect of Long Term Administration of Compound ZiYin Granule on Liv er and Kidney Toxicity of Rats

目的观察复方滋阴颗粒长期大剂量给药对大鼠肝肾毒性的影响,为后续开发奠定基础。方法选用雌性SPF级大鼠160只,随机分为复方滋阴颗粒低、中、高剂量组和空白对照组,每组40只。每天观察记录动物体征;给药中期(13周)、给药末期(26周)和停药4周(30周),分别每组取10只、20只、10只动物,检测血清生化学指标,肝肾称重并计算脏器系数。结果给药末期,复方滋阴颗粒高剂量组肝脏、肾脏系数均显著升高(P<0.5)。给药中期,较空白对照组,颗粒高剂量组ALT、AST、ALP水平显著降低;给药末期,颗粒高剂量组ALT、ALP水平显著降低;低、中、高剂量组AST、TPIL水平显著降低(P<0.5)。恢复期,以上变化指标均与空白对照组无明显差异。结论复方滋阴颗粒大剂量长期给药影响肝脏酶代谢,对肝肾功能有一定影响,停药可恢复。因此,临床长期应用复方滋阴颗粒需注意肝肾功能监测。

OBJECTIVE To observe the liver and kidney toxicity of rats under long-term large dose administration of Compound ZiYin Granule(CZG),then to lay the foundation for the subsequent development.METHODS A total of 160 female SPF rats were randomly divided into CZG low,medium,high dose group and negative control group,with 40 rats in each group.Observed and recorded the clinical signs of the rats every day;after the mid of administration(13 th week),the end of administration(26 th week)and 4 weeks of withdrawal(30 th week),10,20 and 10 rats were operated from each group,respectively,then serum biochemical indexes were detected,liver and kidney were weighed and organ coefficients were calculated.RESULTS At the late stage of administration,the coefficients of liver and kidney in the high dose group of CZG were significantly increased(P<0.5).At the middle stage of administration,ALT,AST and ALP were significantly decreased in high-dose group compared to negative control group;At the late stage of administration,the levels of ALT and ALP in granule high-dose group were significantly decreased while AST and TPIL levels were significantly decreased of each dose group(P<0.5).The above changes had no significant difference with the negative control group during the recovery period.CONCLUSION Long-term administration of CZG with large doses affected liver enzyme metabolism and hepatorenal function,which could be recovered after drug withdrawal.Therefore,the monitoring of liver and kidney function should be concerned during its long-term clinical application.