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目的探讨长效人胰升糖素样肽-1(GLP-1)类似物-利拉鲁肽对2型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)大鼠的脂代谢相关基因mRNA表达的影响。方法健康雄性8周龄SD大鼠36只,按随机数字表法分为三组(每组12只):正常对照组(NC组)、模型组(MC组)及GLP组。NC组喂以常规饲料;MC组喂以高脂高糖饲料,并一次性腹腔注射链脲佐菌素(STZ,30 mg/kg);GLP组喂以高脂高糖饲料,并一次性腹腔注射STZ(30 mg/kg)及腹部皮下注射利拉鲁肽(0.4 mg/kg,1次/d),三组时限均为4周;MC组和GLP组均在一次性注射STZ 4周后检测血糖,判断是否成功建立T2DM模型。取肝组织病理切片,HE染色后光镜下观察肝细胞脂肪变性情况。采用实时荧光定量PCR方法检测肝脏组织脂代谢相关靶基因-脂肪酸合酶(FAS)、乙酰辅酶A羧化酶(ACC-a)、载脂蛋白β100(apoβ100)的mRNA表达,并检测糖脂代谢相关生化指标。结果 MC组及GLP组各成功建立T2DM模型大鼠11只及12只。NC组未见肝细胞脂肪变性,MC组、GLP组均见明显肝细胞脂肪变性,但GLP组程度明显低于MC组。GLP组大鼠血浆空腹血糖(FBG)和空腹胰岛素(FINS)水平,血浆总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和游离脂肪酸(FFAs)水平均较MC组明显降低,高密度脂蛋白胆固醇(HDL-C)水平则较MC组明显升高(P均<0.05);与NC组比较,MC组与GLP组大鼠肝组织FAS、ACC-a mRNA相对表达量均显著升高(P均<0.01),而GLP组上述指标明显低于MC组(P均<0.01);MC组与GLP组大鼠肝组织apoβ100相对表达量均低于NC组(P均<0.01),但GLP组高于MC组(P<0.01)。结论利拉鲁肽可能通过下调脂代谢相关基因的表达,从而改善脂质代谢紊乱,减缓NAFLD发病的进程。
Objective To investigate the mRNA expression of lipid metabolism related genes in long-acting human glucagon-like peptide-1 (GLP-1) -liraglutide in type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) Impact. Methods Thirty - six male Sprague - Dawley (SD) rats, 8 weeks old, were randomly divided into three groups (n = 12): normal control group (NC group), model group (MC group) and GLP group. The rats in NC group were fed with normal diet. The rats in MC group were fed with high-fat and high-sugar diet and STZ was injected intraperitoneally (STZ 30 mg / kg). The rats in GLP group were fed with high-fat and high- The animals were injected with STZ (30 mg / kg) and subcutaneous liraglutide (0.4 mg / kg, once daily) for 4 weeks. The MC and GLP groups were given STZ for 4 weeks Blood glucose test to determine whether the successful establishment of T2DM model. Hepatic histopathological sections were taken and stained with HE to observe the fatty degeneration of hepatocytes. Real-time fluorescent quantitative PCR was used to detect mRNA expression of lipid metabolism related target genes-fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC-a) and apolipoprotein 100 (apoβ100) in liver tissue, Related biochemical indicators. Results In the MC group and the GLP group, 11 and 12 T2DM rats were successfully established. No hepatic steatosis was observed in NC group, and steatosis was observed in both MC and GLP groups, but the GLP group was significantly lower than MC group. The levels of fasting blood glucose (FBG) and fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and free fatty acids (FFAs) (P <0.05). Compared with NC group, the levels of FAS, ACC-a in liver tissue of MC group and GLP group were significantly lower than those in MC group (P <0.01), while the above indexes in GLP group were significantly lower than those in MC group (P <0.01). The relative expression of apoβ100 in MC group and GLP group was lower than that in NC group (All P <0.01), but the GLP group was higher than the MC group (P <0.01). Conclusion Liraglutide may reduce the lipid metabolism related disorders by decreasing the expression of lipid metabolism related genes and alleviating the pathogenesis of NAFLD.