GLP-1对非酒精性脂肪肝病大鼠胰岛素抵抗及PKCε的影响

发布时间：2018-06-07 16:25

本文选题：胰高血糖素样肽 + 非酒精性脂肪肝　；参考：《中国病理生理杂志》2015年04期

【摘要】：目的:探讨胰高血糖素样肽1(GLP-1)对非酒精性脂肪肝病SD大鼠的治疗作用及可能的机制。方法:32只SPF级雄性SD大鼠(体重约130 g)随机抽取21只予高脂饮食(88%普通饲料+10%猪油+2%胆固醇),余下11只予普通饲料饮食作为空白对照组;12周后,将高脂饮食大鼠随机分为2组,每组10只:高脂组予高脂饮食并腹腔注射等体积的无菌生理盐水,治疗组予高脂饮食并腹腔注射利拉鲁肽(GLP-1类似物)注射液(0.6mg·kg-1·d-1)。治疗4周后处死全部大鼠抽取静脉血并取肝脏组织。全自动生化仪检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、甘油三酯(TG)、总胆固醇(TC)及葡萄糖(GLU)含量;ELISA法测定血清胰岛素含量。石蜡包埋肝组织做病理切片及HE染色;real-time PCR法测定肝组织蛋白激酶Cε(PKCε)mRNA的表达,Western blot测定肝组织胞浆PKCε蛋白表达。结果:与正常对照组相比,高脂组的ALT、AST、TG、TC、胰岛素抵抗指数及肝脂数均明显升高;GLP-1治疗组与高脂组相比ALT、AST、TG、TC、胰岛素抵抗指数及肝脂数均下降,差异有统计学意义(P0.05);real-time PCR及Western blot结果提示高脂组PKCεmRNA及蛋白表达减少(P0.05);GLP-1治疗组PKCεmRNA及蛋白表达增多(P0.05)。结论:GLP-1类似物可改善非酒精性脂肪肝的脂质代谢及胰岛素抵抗,该过程可能与PKCε有关。
[Abstract]:Aim: to investigate the therapeutic effect of glucagon like peptide 1 (GLP 1) on non-alcoholic fatty liver disease (SD) and its possible mechanism. Methods Twenty one male Sprague-Dawley rats (weight about 130g) were randomly selected from 32 SPF grade male SD rats. Twenty one rats were given a high-fat diet of 88% lard and 2% cholesterol. The remaining 11 rats were given normal diet as control group for 12 weeks. Rats with high fat diet were randomly divided into two groups, 10 rats in each group: high fat diet and intraperitoneal injection of aseptic saline of the same volume, and treatment group with high fat diet and intraperitoneal injection of Lilalutide GLP-1 analogue) injection of 0.6 mg kg-1 d -1. After 4 weeks of treatment, all the rats were killed to take venous blood and liver tissue. Serum alanine aminotransferase (alt), aspartate aminotransferase (AST), triglyceride (TGG), total cholesterol (TC) and glucose glu (GLU) in serum were detected by automatic biochemical instrument. The expression of protein kinase C (PKC) 蔚 -PKC 蔚 in liver tissue was detected by real-time PCR method and the expression of PKC 蔚 protein in cytoplasm of liver tissue was determined by Western blot. Results: compared with the normal control group, the alt ASTGG TC, insulin resistance index and liver fat number in the hyperlipidemia group were significantly higher than those in the hyperlipidemia group. Compared with the hyperlipidemia group, the alt AST TGG TC, the insulin resistance index and the liver fat number in the GLP-1 group were significantly lower than those in the hyperlipidemia group. The results of real-time PCR and Western blot showed that the expression of PKC 蔚 mRNA and protein in hyperlipidemia group was decreased, and the expression of PKC 蔚 mRNA and protein in GLP-1 group was increased. Conclusion the PKC 蔚 may be involved in the improvement of lipid metabolism and insulin resistance in nonalcoholic fatty liver by the addition of 1: GLP-1 analogue.
【作者单位】：南方医科大学;广东省人民医院广东省医学科学院广东省老年医学研究所消化科;
【基金】：广东省自然科学基金资助项目(No.S2012010010953)
【分类号】：R575.5

【参考文献】