机构地区:[1]广州中医药大学第一附属医院妇儿中心产科,广东广州510405 [2]广州中医药大学第三附属医院妇科,广东广州510405
出 处:《中药新药与临床药理》2020年第12期1416-1421,共6页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:广东省科技厅课题(2017ZC0151)。
摘 要:目的建立妊娠期肝内胆汁淤积症(ICP)大鼠动物模型,并探究茵陈蒿汤干预对于其血清生化指标及肝组织病理改变的影响。方法将40只SPF级中期妊娠(孕10~14 d)Wistar大鼠,随机分为A组30只、B组10只。对A组30只大鼠颈部皮下连续注射5 d苯甲酸雌二醇注射液及黄体酮注射液,进行模型复制,再将模型复制成功的25只随机分为茵陈蒿汤组12只、模型组13只;同时将上述未作模型复制处理的B组10只大鼠标记为对照组。模型组及对照组大鼠予以生理盐水(2 mL·次^-1·d^-1),茵陈蒿汤组大鼠予以茵陈蒿汤水煎剂(1.35 g·kg^-1·d^-1),连续灌服14 d后,对谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、总胆汁酸(TBA)等生化指标进行检测;通过光学显微镜观察大鼠肝脏结构及细胞形态变化,并进行肝脏Knodell组织学活动指数(HAI)评分比较。结果与对照组比较,模型组ALT、AST、TBIL、TBA及肝脏Knodell组织学活动指数(HAI)评分均明显升高(P<0.05)。与模型组比,茵陈蒿汤组血清生化指标ALT、AST、TBIL、TBA及HAI评分均明显低于模型组,且差异有统计学意义(P<0.05)。结论苯甲酸雌二醇及黄体酮可诱导妊娠中期大鼠发生血清生化指标ALT、AST、TBIL、TBA升高以及肝脏组织病理改变,可作为一种稳定、有效的妊娠期肝内胆汁淤积症大鼠模型复制方法。茵陈蒿汤可有效降低妊娠期肝内胆汁淤积症大鼠血清ALT、AST、TBIL、TBA水平,同时对肝组织病理及肝功能的改善具有明显的治疗作用。Objective To establish the rat models of intrahepatic cholestasis of pregnancy(ICP),and explore the effect of Yinchenhao decoction on liver function and pathological changes.Methods Forty Wistar rats with middle pregnancy for 10-14 days were randomly divided into A(30 rats)and B(10 rats)groups.Thirty rats in group A were injected subcutaneously 5 days with estradiol benzoate combined and progesterone for modeling.Twenty-five rat models that met the requirements of this experiment were successfully obtained.Then,they were randomly assigned into 12 rats in the Yinchenhao decoction group and 13 rats in the model group.At the same time,10 rats in group B without modeling were regarded as the control group.Rats in model group and control group were injected with physiological saline(2 mL every time)for 14 days;while the rats in Yinchenhao decoction group were given Yinchenhao water decoction by gavage(1.35 g·kg^-1·d^-1)for 14 days.The levels of serum alanine transarninase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)and total bile acid(TBA)were detected after medication.The changes in structure and cell morphology of rats’livers were observed by optical microscope,and the liver Knodell histological activity index(HAI)score was compared.Results Compared with the control group,the ALT,AST,TBIL and TBA of the model group and the Yinchenhao decoction group were significantly increased(P<0.05).Compared with the model group,the ALT,AST,TBIL and TBA and HAI of the Yinchenhao decoction group were significantly decreased(P<0.05).Conclusion Estradiol benzoate and progesterone can induce the increase of serum biochemical indexes ALT,AST,TBIL,TBA and liver tissue pathological changes in rats in the middle pregnancy.They can be used as a stable and effective method for modeling ICP in rats.Yinchenhao decoction can effectively reduce the serum ALT,AST,TBIL and TBA levels in rats with ICP,and it has obvious therapeutic effects on the improvement of liver tissue pathology and liver function.
关 键 词:茵陈蒿汤 妊娠期肝内胆汁淤积症 肝功能 动物模型 大鼠
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