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(P<0.05);real-time PCR及Western blot结果提示高脂组PKCεmRNA及蛋白表达减少(P<0.05);GLP-1治疗组PKCεmRNA及蛋白表达增多(P<0.05)。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。
AIM：To observe the therapeutic effect of glucagon-like peptide 1 （GLP-1） analog on nonalcoholic fatty liver disease of rats and to investigate the underlying mechanism.METHODS：SD rats （n=21） were used to estab-lish a nonalcoholic fatty liver disease model by feeding a high fat diet for 12 weeks, and other 11 rats were fed with a normal diet for 16 weeks.The model rats were randomly divided into 2 equal groups：one group was treated with glucagon-like pep-tide 1 analog （0.6 mg· kg-1 · d-1 ） by intraperitoneal injection for 4 weeks, the other group using saline as a control.Af-ter treatment, fasting blood glucose, serum insulin, blood lipids, liver function and the pathological changes of the hepatic tissues were evaluated and the expression of PKCεat mRNA and protein levels in the liver tissues was detected by real-time PCR and Western blot, respectively.RESULTS：Compared with model group, the intervention of GLP-1 significantly re-duced insulin resistance index （HOMA-IR）, improved the liver function （P〈0.05）, decreased the liver index and blood lipids （P〈0.05）.HE staining showed obvious pathological changes of the hepatic tissues in model group, and the inter-vention of GLP-1 significantly reduced lipid droplets in the hepatocytes and improved the structural damage of the liver.The expression of hepatic protein kinase Cε（ PKCε） at mRNA and protein levels significantly decreased which were reversed by＇nbsp;treating with GLP-1.CONCLUSION：GLP-1 shows good therapeutic effect on nonalcoholic fatty liver disease of rats, pos-sibly by controlling lipid metabolism and reducing insulin resistance, which may be related to PKCεexpression.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2015年第4期690-694,共5页
Chinese Journal of Pathophysiology
基金
广东省自然科学基金资助项目(No.S2012010010953)
