复方木鸡颗粒对DEN致大鼠肝炎的量效初步研究

The dose-effect preliminary study of Compound Muji Granules on hepatitis induced by DEN in rats

目的评价复方木鸡颗粒对二乙基亚硝胺(DEN)致大鼠肝炎模型的药效作用,初步探讨量效关系。方法将SD大鼠随机分为空白对照组、模型组、联苯双酯组(阳性对照药,0.15 g·kg^(-1))及复方木鸡颗粒(0.04、0.12、0.36、1.08、3.24 g·kg^(-1))5个剂量组(n=12)。除空白对照组外,其余各组每周1次口服灌胃二乙基亚硝胺(70 mg·kg^(-1)),同时给予各组大鼠相应的药物,每天灌胃给药1次,连续4周。测定大鼠的体重、肝指数,运用酶联免疫法(ELISA)检测血清中天门冬氨酸氨基转移酶(AST)、谷丙转氨酶(ALT)的含量,苏木精-伊红(HE)染色评价各组大鼠肝脏病理改变,探讨量效关系。结果与模型组比较,复方木鸡颗粒各剂量组大鼠的肝指数、血清中天门冬氨酸氨基转移酶、谷丙转氨酶的含量明显下降(P<0.01),体重明显升高(P<0.01或0.05),能够明显改善肝细胞状态和炎性细胞浸润等病理变化。其中复方木鸡颗粒0.12 g·kg^(-1)组生理、生化、病理指标均有极显著性差异,药效明显,复方木鸡颗粒0.04g·kg^(-1)、3.24 g·kg^(-1)组疗效较优于复方木鸡颗粒0.36 g·kg^(-1)、1.08 g·kg^(-1)组。结论本实验验证了复方木鸡颗粒对二乙基亚硝胺诱导大鼠肝炎药效作用的基础上,初步探讨量效关系,为其临床合理用药提供依据,同时也为其治疗肝病不同发展阶段(肝炎、肝硬化、肝癌)临床最佳给药剂量的差异化研究奠定实验基础。

Objective To evaluate the effectiveness of Compound Muji Granules on hepatitis model induced by DEN in rats,and preliminary explore dose-effect relationship. Methods The SD rats were randomly divided into normal control group,model group,bifendatatum group（ positive control drug,0.15 g·kg^-1） and Compound Muji Granules groups of five different doses（ 0.04,0.12,0.36,1.08,3.24 g·kg^-1）,n= 12.Except for normal control group,DEN（ 70 mg·kg^-1） were intragastrically administered to other groups rats once per week,at the same time the corresponding drugs were intragastrically administered to each group rats once a day for four weeks.The body weight,liver weight index were recorded,the serum contents of aspartate aminotransferase（ AST）,alanine aminotransferase（ ALT） were detected by enzyme linked immunosorbent assay（ ELISA） and HE staining of liver tissue was used to evaluate pathological changes to explore the dose-effect relationship.Results Compared with the model group,each dose groups of Compound Muji Granules liver weight index and contents of AST,ALT in serum were significantly decreased（ P〈0. 01）,and body mass were significantly higher（ P〈0. 01 or0.05）.HE staining showed that hepatocellular morphology and infiltration of inflammatory cells could significantly improve.The effectiveness of Compound Muji Granules 0.12 g·kg^-1group was obvious,there were extremely significant differences in physiological,biochemical and pathological indexes. The effectiveness of Compound Muji Granules 0. 04 g · kg^-1,3.24g·kg^-1group were superior to Compound Muji Granules 0.36 g·kg^-1,1.08 g·kg^-1group.Conclusion Based on the effectiveness of Compound Muji Granules on hepatitis model induced by DEN in rats was verified to explore the dose-effect relationship,in order to provide a basis for rational drug in clinical practice and lay experimental foundation for difference of clinical best dose in treating different stages liver disease（ hepatitis,hepatic cirrhosis,hepatocarcinoma）.