PKB/ Akt 在高脂诱导鼠肾脏损害中的作用

目的:通过建立高脂血症大鼠模型,探讨单纯高脂对肾脏的损伤机制以及胰岛素传导通路中的关键酶PKB/Akt(丝氨酸/苏氨酸激酶)在高脂所致肾脏损害中的变化和意义。方法:高脂高胆固醇喂养Wistar雄性大鼠,建立胰岛素抵抗模型。分别在4周、8周、12周测定大鼠的肾功,包括血尿素蛋(BUN),肌酐(CREA);16周时测定甘油三酯(TG),胆固醇(TC),以及血糖(FBS)和胰岛素(FINS)。8周时行胰岛素增敏剂文迪雅(3mg/kg)灌胃干预四周,并行肾脏病理检查,应用免疫组化法监测PKB/Akt在肾脏的表达。结果:高脂喂饲大鼠4周后,进食量开始减少,体重增加减慢;血BUN、血CREA在4周时已升高,至8周时增加更明显(p<0.001)。文迪雅灌胃四周后肾功改善,但仍高于正常组(p<0.05)。血TG和血TC较正常组升高显著,统计学差异显著(p<0.05)。血胰岛素升高,但胰岛素敏感性降低,胰岛素抵抗指数增加显著,提示胰岛素抵抗形成。肾脏免疫组化PKB/Akt的表达呈现为在肾小球和肾小管分布不均,出现PKB/Akt在损伤较重的肾小球不表达,而在损伤较轻的肾小管表达减弱的现象。结论:饮食诱导的高脂血症可导致健康大鼠产生脂质肾毒性损害以及肾功的降低,并可产生胰岛素抵抗。胰岛素传导通路的损害在肾小球和肾小管表达不同,说明其可能是产生肾脏损伤及胰岛素抵抗的又一原因。胰岛素增敏剂可改善胰岛素抵抗及肾功。

Effects of PKB/ Akt in the Progression of Renal Injury Induced by High Fat

Objective: To investigate the effects of the key enzyme PKB/ Akt( serine- threorine kinase) in the common pathway of insulinin the progression of renal injury induced by high fat( HF) and its mechanism through the establishment of rat models with hyperlipidemia. Methods:50 Wistar male rats were randomly divided into five groups: ?? normal control group( n= 10) ; ?? 4- week HF- feeding group( n= 10) ; ??8- week HF- feeding group( n= 10) ; ??8- week HF- feeding plus 4- week Avandia group( n= 10) ; ?? 16- week HF- feeding group( n=10) . After the establishment of insulin resistance models, a series of renal functions including blood urea nitrogen ( BUN) and creatinine( CREA)of these models were measured at the 4th week, the 8th week and the 12th week separately. Trig1ycerides( TG) , total cholesterol( TC) , fastingblood sugar( FBS) and fasting insulin( FINS) were measured at the 16th week. These rat models were influenced by feeding with Avandia ( i. e. aninsulin sensitizer) ( 3mg/ kg, intergastricly for 4 weeks ) from the 8th week and were taken renal pathological examination using the expression ofPKB/ Akt in kidney monitoring by immunohistochemical method. Results: After being fed with high fat and high cholesterol diet for 4 weeks,Rats?? taking food amount started to reduce and the increase of their weights slowed down. BUN and CREA had already risen at the 4th week, theincrease was more obvious at the 8th week ( P< 0. 001) . The renal function was improved after rats were fed with Avandia intergastricly for 4weeks, but the proportion was still higher than that of the control group( P< 0. 05) . The TC and TG in blood were markedly higher than those ofthe control group, and the statistic difference is remarkable ( P< 0. 05) . The level of insulin in blood rose but insulin sensitivity reduced. The indexof insulin resistance rose remarkbly. It pointed out the taking shape of the insulin resistance. The expression of the PKB/ Akt of renal immunohistochemicalshowed the uneven distribution in glomerulus and renal tubules. The expression of the PKB/ Akt disappeared in the seriously injuredglomerulus and weakened in the lightly injured renal tubules. Conclusions: The hyperlipidemia induced by high fat diet could cause healthy ratssuffer from lipid nephrotoxic damage, renal function reducing and the insulin resistance. The expressions of the damage of common pathway of insulinare different in glomerulus and renal tubules, which shows that it could be another reason why renal damage and the insulin resistanceformed, but insulin sensitizer can improve insulin resistance and renal function.