生姜乙醇提取物改善果糖所致大鼠脂肪肝的作用机制研究

Mechanism of Ginger Ethanol Extract in Improving Fructose-induced Rat Fatty Liver

目的观察姜提取物改善果糖所致大鼠脂肪肝的作用,并探讨其可能的作用机制。方法取SD大鼠24只,随机分为4组,每组6只,即正常对照组(给予正常饮食饮水),模型组(给予10%果糖水),姜提取物低、高剂量组20,50 mg·kg^(-1),给予姜提取物灌胃,连续28 d。用酶法和ELISA检测血浆葡萄糖、甘油三酯(TG)、胆固醇(TC)和胰岛素含量,苏木精-伊红(HE)染色和油红-O染色观察肝脏组织中的脂肪沉积程度,RT-PCR和Western blot法检测肝脏相关基因和蛋白表达。结果姜提取物逆转了果糖过量消耗引起的大鼠肝脏甘油三酯的过度堆积(P<0.05)、肝细胞空泡化的增加和肝脏油红-O染色面积的增加(P<0.05)。然而,姜提取物并不影响大鼠食物摄入量和体质量。姜提取物能够抑制肝脏二脂酰甘油酰基转移酶(DGAT)-2 mRNA和蛋白的过表达(P<0.05),但对肝X受体(LXR)、DGAT-1、单酰甘油酰基转移酶(MGAT)-1、MGAT-2、激素敏感脂肪酶(HSL)和脂肪甘油三酯脂肪酶(ATGL)mRNA的表达无影响。结论姜提取物可能通过抑制介导肝脏甘油三酯生物合成的关键酶DGAT-2的过表达,从而改善果糖所致大鼠脂肪肝。

Objective To observe the effect of ginger ethanol extract（GEE）on improving fructose-induced fatty liver and to explore the possible mechanism. Methods Twenty-four male SD rats were randomized into normal group,model group, and low- and high-dose GEE（20, 50 mg·kg^（-1）, ig, for 4 weeks） groups, 6 rats in each group.Enzymatical method and ELISA were used for the examination of plasma glucose,triglyceride（TG）,total cholesterol（TC） and insulin. Fat deposit in rat liver was observed after HE staining and Oil Red O staining. The mRNA and protein expression revels of fatty liver associated enzymes were analyzed by real-time PCR and Western blot respectively. Results GEE attenuated the accumulation of TG in rat liver of the model group, and reduced the increases of hepatocyte vacuolization and Oil Red O staining area in the liver（P〈0.05）. But GEE had no effect on food intake and body weight. The anti-steatotic effect of GEE treatment was accompanied by the suppression of hepatic overexpression of diacylglycerol acyltransferase（DGAT）-2 at the mRNA and protein levels（P〈0.05）. But hepatic expression of liver X receptor,DGAT-1,monoacyglycerol acyltransferase（MGAT）-1,MGAT-2,hormone-sensitive lipase and adipose triglyceride lipase remained unchanged after GEE treatment. Conclusion GEE can improve fructose-induced fatty liver in rats alternatively by inhibiting hepatic overexpression of DGAT-2 that mediates triglyceride biosynthesis.