ibrolipim对糖尿病小型猪肝脏PKBβ/Akt2表达的影响  

Effect of Lipoprotein Lipase Activator ibrolipim on Expression of Protein Kinase-B in Hepatic of Diabetic Miniature Pigs

作　　者：魏寒松[1] 余坚[2] 刘毅[1] 李宏光[1] 陈安平[3] 尹卫东[3] 王宗保[2] 

机构地区：[1]南华大学生物化学与分子生物学教研室,衡阳421001 [2]南华大学实验动物学部 [3]南华大学心血管病研究所

出　　处：《医学研究杂志》2008年第8期50-54,共5页Journal of Medical Research

基　　金：湖南省科技厅科研项目[2006TP3015]

摘　　要：目的采用高脂高糖高胆固醇饮食喂养的方法建立广西巴马小型猪糖尿病动物模型。研究合成化合物ibrolipi(NO-1886)对肝脏PKBβ/Akt2表达变化的影响,探讨ibrolipim改善胰岛素抵抗、治疗糖尿病的可能机制。方法15头雄性广西巴马小型猪按体重随机分为3组:正常对照组(n=5)饲以正常饲料;高脂高糖高胆固醇组(n=5)饲以高脂高糖高胆固醇饲料;加药组(n=5),HFSCD饲料中加入1.0%NO-1886。每月末测定血糖、甘油三酯、胰岛素和口服葡萄糖耐量实验。第5个月末取部分肝脏组织用western blotting和免疫组织化学方法检测Akt2蛋白的表达。结果CD组血糖、甘油三酯、胰岛素水平正常,葡萄糖耐量实验(OGTT)血糖清除和胰岛素分泌有效、及时;与CD组相比较,HFSCD组血糖和甘油三酯胰岛素水平明显升高,糖耐量减低;HFSCD+NO-1886组与HFSCD组相比,血糖、甘油三酯和胰岛素水平明显降低,OGTT葡萄糖清除和胰岛素分泌近似CD组。CD组肝脏Akt2蛋白表达量较高;HFSCD组Akt2表达量减少(P<0.05);HFSCD+1%NO-1886组Akt2蛋白表达较HFSCD明显增高(P<0.05)但低于CD组。结论饮食诱导的糖尿病小型猪肝脏组织Akt2表达降低;NO-1886能够上调肝脏Akt2蛋白的表达,改善胰岛素抵抗。Objective To investigate the effect of lipoprotein lipase （LPL） activator NO-1886 on the protein expression of the protein kinase-B （PKB/Akt） in liver of diabetic minipigs induced by high-fat/high-sucrose/high-cholesterol diet. Methods Fifteen Guangxi Bama minipigs were randomized into three groups： CD group （n = 5） , HFSCD group （n = 5） , and HFSCD＋NO-1886 group （ n = 5 ）. plasma glucose, insulin, triglyceride and oral glucose tolerance test（OGTT） were measured each month following overnight fasting. The pigs were sacrificed at the end of month 5. liver was obtained for histological preparations, the protein expression of Akt2 in liver was measured by western blotting and immunohistochemistry. Results Compared with CD group, the level of plasma glucose, triglyceride and insulin were evidently increased in the HFSCD group. After supplementing NO -1886 into HFSCD, the concentration of plasma glucose, triglyceride and insulin obviously decreased compared with the HFSCD group. The expression of Akt2 decreased in HFSCD group, but NO-1886 can increased the expression of Akt2 on liver. Conclusion NO-1886 can decrease the level of plasma glucose, triglyceride and insulin and up-regulate the protein expression of Akt2 in diabetic minipigs induced by the high-fat/high-sucrose/high-cholesterol diet.

关 键 词：NO-1886 糖尿病 胰岛素抵抗 肝脏 蛋白激酶-B 小型猪 

分 类 号：R363[医药卫生—病理学] R734.2[医药卫生—基础医学]