GLP-1下调非酒精性脂肪肝大鼠SOCS-3和SREBP-1c的表达

GLP-1 down-regulates mRNA expression of SOCS-3 and SREBP-1c in rats with nonalcoholic fatty liver disease

目的:探讨胰高血糖素样肽-l(GLP-1)对非酒精性脂肪肝大鼠SOCS-3和SREBP-1c mRNA表达的影响。方法:将雄性SD大鼠32只随机分为正常对照(NC)组、高脂(HF)组和HF+利拉鲁肽(Lira)组。HF组和HF+Lira组给予高脂饲料喂养16周,HF+Lira组高脂喂养12周后,给予Lira 600μg·kg^(-1)·d^(-1)腹腔注射4周。在16周末处死大鼠。全自动生化仪检测血清ALT、AST、甘油三酯(TG)和总胆固醇(TC);GPO-PAP法测定肝脏TG含量;酶联免疫法测定空腹胰岛素,并计算胰岛素抵抗指数(HOMA-IR);光学显微镜下观察肝脏病理变化;RTqPCR法测定肝组织SOCS-3和SREBP-1c的mRNA表达水平。结果:与NC组相比,HF组血清ALT、AST、TG、TC、肝TG、FINS及HOMA-IR均明显升高(P<0.01);HF+Lira组与HF组相比,血清的ALT、AST、TG、TC、肝TG、FINS及HOMA-IR均下降,差异有统计学显著性(P<0.05)。HF组肝组织SOCS-3和SREBP-1c的mRNA表达水平较NC组显著增强(P<0.01);HF+Lira组较HF组SOCS-3和SREBP-1c的mRNA表达显著下降(P<0.05)。结论:Lira可能通过下调肝组织SOCS-3和SREBP-1c的mRNA表达,改善IR,减少肝脏TG沉积,从而对非酒精性脂肪性肝病起到治疗作用。

AIM： To investigate the effects of glucagon-like peptide-1（ GLP-1） on mRNA expression of SOCS-3 and SREBP-1c in the rats with nonalcoholic fatty liver disease. METHODS： Male SD rats were randomly divided into normal control（ NC） group,high fat（ HF） group and HF ＋ liraglutide（ Lira） group. The rats in HF group and HF ＋Lira group were given high-fat diet for 16 weeks. After 12 weeks of high-fat diet feeding in HF ＋ Lira group,Lira（ 600 μg·kg^（-1）·d^（-1）） was intraperitoneally injected for 4 weeks. At the end of the 16 th week,the rats were killed. The pathological changes of the liver were observed under optical microscope. The serum levels of alanine aminotransferase（ ALT）,aspartate aminotransferase（ AST）,triglyceride（ TG） and total cholesterol（ TC） were detected by automatic biochemical analyzer. TG contents of liver were measured by GPO-PAP method. The fasting insulin（ FINS） was determined by ELISA,and insulin resistance index was assessed by homeostasis mode assessment（ HOMA-IR）. The mRNA expression of SOCS-3 and SREBP-1c in the liver tissues was detected by RT-qPCR. RESULTS： Compared with NC group,HOMA-IR,TG of liver,and the serum levels of ALT,AST,TG,TC and FINS in HF group were obviously increased（ P〈0. 01）. Compared with HF group,HOMA-IR,TG of liver,and the serum levels of ALT,AST,TG,TC and FINS in HF ＋ Lira group were all obviously decreased（ P〈0. 05 or P〈0. 01）. The mRNA expression of SOCS-3 and SREBP-1c in HF group was significantly higher than that in NC group（ P〈0. 01）. The mRNA expression of SOCSV3 and SREBP-1c in HF ＋ Lira group was significantly decreased as compared with HF group（ P〈0. 05）. CONCLUSION： Liraglutide may improve the IR and reduce TG of liver through decreasing the mRNA expression of SOCS-3 and SREBP-1c,so as to play a therapeutic role in nonalcoholic fatty liver disease.