小檗碱对梗阻性黄疸大鼠肝细胞线粒体能量代谢的保护作用

Protective Effect of Berberine on Mitochondrial Energy Metabolism of Liver in the Rat with Obstructive Jaundice

目的:探讨小檗碱(BBR)对梗阻性黄疸大鼠肝细胞线粒体能量代谢的保护作用及其机制。方法:将雄性Wistar大鼠45只随机分为3组,A(Sham)组:假手术组;B(BDL)组:胆道结扎组;C(BDL+BBR)组:胆道结扎同时小檗碱干预组。术后7d取血清检测总胆红素(TBIL)、直接胆红素(DBIL)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST),检测肝细胞线粒体内丙二醛(MDA)、超氧化物歧化酶(SOD)、ATP、ADP和AMP含量并计算能荷(EC),Western blot检测肝组织AMPK、PGC-1α表达。结果:B组与A组比较:血清ALT、AST含量升高,肝组织p-AMPK、PGC-1α表达下降,肝细胞线粒体内MDA、AMP含量升高,SOD、ATP、ADP、EC含量降低(P<0.05);C组与B组比较:血清ALT、AST含量降低,肝组织p-AMPK、PGC-1α表达升高,肝细胞线粒体内MDA、AMP含量降低,SOD、ATP、ADP、EC含量升高(P<0.05)。结论:小檗碱可能通过激活AMPK/PGC-1α信号途径,减轻梗阻性黄疸时肝细胞氧化损伤,改善能量代谢。

Objective： To investigate the protective effect of berberine（BBR） on mitochondrial energy metabolism of liver in the rat with obstructive jaundice. Methods： Forty five rats were divided randomly into groups of sham operation （Sham, group A）, bileduct-ligation（BDL, group B） and bileduct-ligation（BDL＋BBR, group C）. All rats were sacrificed on the 7th day after BDL and the blood and liver tissue samples were obtained. The levels of serum ALT,AST,TBIL,DBIL and the levels of malondialdehyde（MDA）, superoxide dismutase（SOD）, ATP, ADP, AMP in rat liver＇ s mitochondrion were detected. The expression of the AMPK and PGC-1α proteins were analyzed by Western blotting. Results： Compared with those in group A, the levels of the p-AMPK and PGC-1α proteins, SOD, ATP, ADP, EC were lower （ P 〈 0.05）, but the ALT, AST, MDA, AMP were higher in group B（P〈0.05）. The levels of the p-AMPK and PGC-la proteins,SOD,ATP, ADP,EC were higher（P〈0.05）, while the ALT, AST, MDA, AMP were lower（P〈0.05） in group C than in group B. Conclusion： The BBR can protect the liver from the peroxide damage and improve mitochondrial energy metabolism by activating AMPK/PGC-lα pathway.