二甲双胍对NAFLD大鼠肝脏脂联素/SIRT1 mRNA表达的影响

Effect of metformin on mRNA expression of adiponectin and SIRT1 in liver tissue of NAFLD rats

目的观察二甲双胍对高脂饮食诱导NAFLD大鼠肝脏脂联素和SIRT1基因表达的影响,探讨其潜在的机制。方法将34只SD大鼠随机分为2组:对照组(NC组,12只,给予普通饲料)、高脂组(HF组,22只,给予高脂饮食),喂养8周后两组各随机抽取6只;证实NAFLD模型建立后,将剩余HF组大鼠随机分为二甲双胍干预组(HF+M组,8只)、高脂组(HF1组,8只)及对照组(NC1组,6只),均给予等体积生理盐水,灌胃8周后,测定空腹血糖(FBG)、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)、三酰甘油(TG)、游离脂肪酸(FFA)及肝脏TG含量,测定胰岛素(FINS)水平,并计算胰岛素抵抗指数(HOMA-IR);HE染色观察肝脏病理形态学变化;采用Real-time PCR法检测肝组织脂联素、SIRT1、AMPK-αmRNA表达。结果高脂喂养8周后,HF组大鼠NAFLD模型建立,伴明显胰岛素抵抗。HF+M组大鼠血清TC、TG、FFA、FBG、ALT、AST、肝脏TG含量及HOMA-IR低于HF1组(P<0.05),血清脂联素较HF1组升高(P<0.05),肝脏脂肪变较HF1组有所改善;与HF1组比较,HF+M组肝脏SIRT1、AMPK-αmRNA表达增加(P<0.05)。结论二甲双胍可减轻NAFLD大鼠胰岛素抵抗及肝脏TG沉积,其机制可能与通过升高血清脂联素水平,进而激活SIRT1/AMPK信号通路有关。

Objective To observe the effect of metformin on mRNA expression of liver adiponectin and SIRT1 in NAFLD rats induced by high-fat diet,and discuss the possible mechanisms.Methods Totally 34 SD rats were randomly divided into two groups：normal control group（NC group,n = 12,normal diet） and high fat group（HF group,n = 22,high fat diet）.Six rats were randomly selected from two groups respectively after being fed for 8 weeks to confirm that the NAFLD model had been established.The other NAFLD rats in HF group were divided into metformin treatment group（HF ＋ M group,n =8） and HF1 group（n =8）.Rats in HF ＋ M group and NC1 group were respectively given intragastric administration of metformin 500 mg/（kg·d） and equal volume of saline for 8 weeks.The levels of serum alanine transferase（ALT）,aspartate aminotransferase（AST）,total cholesterol（TC）,total glyceride（TG） and free fatty acid（FFA） were detected after 8 weeks of gavage,the fasting serum glucose and insulin（FINS）level were measured and the insulin resistance index（HOMA-LR） were calculated.The liver pathological changes were observed by HE staining,and the adiponectin,SIRT1 and AMPK-α mRNA were measured by using real time PCR.Results After 8 weeks of high-fat diet,the NAFLD rat model of HF group which was complicated with insulin resistance was established.Compared with HF1 group,the levels of serum TC,TG,FFA,FBG,ALT and AST,the liver TG content and HOMA-IR in HF ＋ M group were lower（P〈0.05）,while the level of adiponectin was higher（P〉0.05）,and the pathological changes of rats＇ liver were improved.The expression of SIRT1,adiponectin and AMPK-a mRNA in the liver in HF ＋ M group was higher than that of HF1 group（P〈0.05）.Conclusion Metformin can alleviate the insulin resistance and the liver TG deposition of NAFLD rats induced by high-fat diet,the mechanism may be associated with the activation of SIRT1/AMPK signal pathway through up-grading the serum adiponectin level.