小檗碱对非酒精性脂肪肝大鼠肝脏脂肪沉积的改善作用及相关机制研究

目的探究小檗碱对非酒精性脂肪肝(NAFLD)大鼠肝脏脂肪沉积的改善作用及相关机制。方法采用高脂饮食喂养8周的方法建立NAFLD大鼠模型。将成功建立的NAFLD大鼠随机分为模型组(n=18)、阳性对照组(n=18)及实验组(n=18)。另选择18只未加任何干预的正常大鼠作为对照组。阳性对照组大鼠灌胃10 mg·kg-1·d-1罗格列酮,实验组灌胃162 mg·kg-1·d-1小檗碱,对照组与模型组灌胃等量生理盐水,连续干预4周。采用全自动生化分析仪检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TC)、甘油三酯(TG)及血清游离脂肪酸(FFA)含量;采用苏木精-伊红(HE)染色和油红O染色观察大鼠肝脏病理学变化和脂肪沉积情况;采用蛋白质印迹法检测各组大鼠肝组织肝X受体α(LXRα)、脂肪酸合成酶(FAS)蛋白表达。结果对照组、模型组、阳性对照组及实验组大鼠血清ALT水平分别为(45.68±5.64),(71.61±5.25),(54.78±3.82),(63.37±5.16)U·L-1;AST水平分别为(216.24±55.28),(336.56±73.12),(252.42±33.56),(286.48±48.59)U·L-1;TC水平分别为(1.32±0.31),(4.05±1.12),(1.81±0.67),(2.63±0.94)mmol·L-1;TG水平分别为(0.28±0.14),(0.81±0.18),(0.47±0.15),(0.63±0.17)mmol·L-1;FFA水平分别为(227.45±48.16),(446.56±53.72),(271.37±28.87),(319.36±55.64)μmoL·L-1;大鼠肝组织中LXRα蛋白相对表达量分别为0.32±0.11,1.21±0.13,0.41±0.09,0.96±0.04;FAS蛋白相对表达量分别为0.28±0.09,1.28±0.11,0.45±0.08,0.93±0.07,差异均有统计学意义(均P<0.05)。结论小檗碱可改善NAFLD大鼠脂质代谢和肝功能,减轻肝脏组织病变程度,减少脂肪沉积,抑制LXRα/FAS信号通路可能是其作用机制之一。

Study on the improvement effect of berberine on liver fat deposition in rats with non-alcoholic fatty liver and related mechanism

Objective To explore the effect of berberine on the improvement of liver fat deposition in rats with non-alcoholic fatty liver(NAFLD) and related mechanisms.Methods The NAFLD rat models were established by feeding with a high-fat diet for 8 weeks.The successfully established NAFLD rats were randomly divided into the model group(n=18), the active control group(n=18) and the test group(n=18).Another 18 normal rats without any intervention were selected as the control group.Rats in the active control group were intragastrically administered with rosiglitazone(10 mg·kg-1·d-1), rats in the test group were intragastrically administered with berberine (162 mg·kg-1·d-1),the control group and the model group were given the same amount of normal saline for 4 weeks.Serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC),triglyceride(TG) and serum free fatty acid(FFA) were detected by automatic biochemical analyzer;Hepatic pathological changes and fat deposition were observed by hematoxylin-eosin(HE) staining and oil red O staining;Western blotting was used to detect the expression of LXRα and FAS protein in liver tissues.Results The serum ALT levels of the control group,the model group,the active control group and the test group were(45.68 ± 5.64),(71.61 ± 5.25),(54.78 ± 3.82),and(63.37 ± 5.16) U · L-1;The AST levels were(216.24 ± 55.28),(336.56 ± 73.12),(252.42 ± 33.56),(286.48 ± 48.59) U · L-1;The TC levels were(1.32 ± 0.31),(4.05 ± 1.12),(1.81 ± 0.67), and(2.63 ± 0.94) mmol · L-1;The TG levels were(0.28 ± 0.14),(0.81 ± 0.18),(0.47 ± 0.15), and(0.63 ± 0.17) mmol · L-1;FFA levels were(227.45 ± 48.16),(446.56 ± 53.72),(271.37 ± 28.87),(319.36 ± 55.64) μmo L·L-1;The relative expression of LXRα protein in liver tissues were 0.32 ± 0.11,1.21 ± 0.13,0.41 ± 0.09,0.96 ± 0.04,respectively;The relative expression levels of FAS protein were 0.28 ± 0.09,1.28 ± 0.11,0.45 ± 0.08,and 0.93 ± 0.07.the differences were statistically significant(all P < 0.05).Conclusion Berberine could improve lipid metabolism and liver function in NAFLD rats,reduce liver tissue lesions,reduce fat deposition,and inhibiting the LXRα/FAS signaling pathway may be one of its mechanisms.