中文摘要：

目的观察小檗碱对非酒精性脂肪性肝病（NAFLD）大鼠肝组织p38MAPK-STAT3信号通路相关基因及蛋白表达的调控作用,探讨小檗碱防治NAFLD的作用机制。方法取SPF级雄性SD大鼠24只,适应性喂养1周后,随机分为正常组、模型组和小檗碱组（100 mg·kg^-1）,每组8只。除正常组给予基础饲料外,其余两组均采用高脂饮食喂养,建立大鼠NAFLD模型,在施以造模因素的同时,小檗碱组灌胃给药,8周后对肝组织行HE染色和油红O染色。全自动生化仪检测血清总胆固醇（TC）、甘油三脂（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、谷丙转氨酶（ALT）、谷草转氨酶（AST）;ELISA法检测血清及肝组织超氧化物歧化酶（SOD）、丙二醛（MDA）含量;实时荧光定量RT-PCR法检测肝组织p38MAPK、STAT3 mRNA表达量;Western Blotting法检测肝组织蛋白p38MAPK、STAT3及p-p38MAPK、p-STAT3表达水平。结果 8周高脂饮食成功诱导建立了NAFLD实验动物模型,HE染色和油红O染色证实大鼠模型肝组织脂质蓄积严重。与正常组比较,模型组大鼠血清TG、TC含量明显升高（P〈0.05）,肝组织及血清SOD活力明显降低（P〈0.01）,MDA水平明显升高（P〈0.01）,p38MAPK、STAT3 mRNA及p38MAPK、p-p38MAPK、STAT3、p-STAT3蛋白的表达水平均显著升高（P〈0.05,P〈0.01）;与模型组比较,小檗碱组大鼠血清TG、TC含量明显降低（P〈0.05）,肝组织及血清SOD活力明显升高（P〈0.05,P〈0.01）,MDA水平明显降低（P〈0.05,P〈0.01）,p38MAPK、STAT3 mRNA及p-p38MAPK、p-STAT3蛋白表达水平明显下调（P〈0.05）。结论小檗碱可以改善NAFLD模型大鼠肝脏脂肪变性,降低其血清及肝组织氧化应激因子水平,其机制可能是通过激活肝脏p38MAPK-STAT3信号通路相关基因及其蛋白磷酸化水平,改善氧化应激而发挥作用。

英文摘要：

Objective To observe the regulatory effect of berberine on p38MAPK- STAT3 signal pathway related m RNA and protein expression in hepatic tissues of non- alcoholic fatty liver disease（NAFLD） rats and to explore the therapeutic mechanism of berberine for NAFLD. Methods A total of 24 male SD rats at specific pathogen free（SPF）level were fed adaptively for one week and then were randomly divided into three groups,namely normal group,model group and berberine group,8 rats in each group. Except for the the normal group,the other two groups were fed with high- fat diet to establish the NAFLD model. Berberine group was given 100 mg·kg^-1 of berberine hydrochloride tablets by gavage once a day simultaneously. After treatment for 8 weeks,the hepatic issues were analyzed after HE staining and oil red O staining. Triglyceride（TG）, total cholesterol（TC）, high density lipoprotein cholesterol（HDL- C）, low density lipoprotein cholesterol（LDL- C）,alanine aminotransferase（ALT）and aspartate aminotransferase（AST）levels in blood serum were detected with automatic biochemical analyzer. Superoxidase dismutase（SOD） and malondialdehyde（MDA）in the serum and hepatic issues were examined by ELISA method. The expression quantity of p38 MAPK and STAT3 m RNA in hepatic issues was detected by reverse transcription polymerase chain reaction（RT- PCR）,and the expression level of p38 MAPK and STAT3 protein as well as the phosphorylated p38 MAPK and STAT3 protein in hepatic issues was examined by Western blotting. Results NAFLD rat model has been established after the induction of high- fat diet for 8 weeks. Compared with the normal group,hepatic lipid accumulation of model group rats proved severe by histopathological examination;the serum levels of TG and TC were increased significantly（P〈0.05）,SOD activity in liver tissue and serum was significantly decreased（P〈0.01）,MDA level was significantly elevated（P〈0.01）, and the m RNA expression levels of p38 MAPK and STAT3 and protein express