ApoAI/ABCA1途径对糖尿病肾病大鼠的保护作用

Protective Effect of ApoAI/ABCA1 Pathway in Diabetic Nephropathy Rats

目的:观察ApoAI/ABCA1途径对糖尿病肾病炎症反应是否有调节作用。方法:选用SD大鼠40只随机分为4组,每组10只,分别为:正常对照组、糖尿病肾病(DN)组、DN+载脂蛋白-I(ApoA-I)组、DN+绿色荧光蛋白(GFP)组。除正常对照组外,其它3组腹腔注射链脲佐菌素(STZ,65 mg/kg)溶液造糖尿病大鼠模型。DN+ApoA-I组在糖尿病造模成功后尾静脉注射腺病毒AdV-AI;DN+GFP组在糖尿病造模成功后通过尾静脉注射腺病毒Ad V-GFP,方法同DN+ApoA-I组。观察各组大鼠血清肿瘤坏死因子-α(TNF-α)、MCP-1,肾组织抗炎蛋白(锌指蛋白36,TTP)表达及ABCA1 mRNA表达。结果:相对于对照组,DN组、DN+ApoA-I组、DN+GFP组大鼠血清中的TNF-α、MCP-1水平明显上升(P<0.05);相对于DN组,DN+ApoA-I组的TNF-α、MCP-1水平明显下降(P<0.05);相对于对照组,DN组TTP蛋白、ABCA1 mRNA的表达量有所降低(P<0.05);相对于DN组,DN+ApoA-I组大鼠肾组织TTP蛋白、ABCA1 mRNA的表达明显升高(P<0.05);DN+GFP组大鼠TTP蛋白、ABCA1 mRNA的表达与DN组相比无明显变化。结论:ApoA-I/ABCA1途径是体内抗DN炎症激活的关键作用途径,其机制可能通过上调TTP,从而促进多种炎症因子的降解。

Objective To observe the effect of ApoAI/ABCA1 pathway that regulate infl ammation in diabetic nephropathy.Methods The DN rat model was established by injection of streptozotocin（STZ,65 mg/kg）in abdominalcavity.Forty SpragueDawley male rats were randomly divided into 4 groups：normal group,DN group,DN＋ApoA-I group,DN＋GFP group,and then,DN＋ApoA-I group and DN＋GFP group were injected intravenously with AdV-AI or AdV-GFP（1×1011v.p./mice/d）.After 4 weeks,animals were killed.The euzymelinked immunosorbent assay（ELISA）were performed to examine the levels of TNF-α and MCP-1 in serum respectively.The immunohistochemisty was performed to examine the protein expression level of TTP in kidney tissue.The m RNA of ABCA1 in kidney tissue was reverse transcribed and quantified by rea-ltime PCR.Results The levels of TNF-α and MCP-1in serum of DN group,DN＋ApoA-I group,DN＋GFP group were significantly higher than that of normal group（P〈0.05）,and that of DN＋Apo A-I group was significantly lower than that of DN group（P〈0.05）; The expression of TTP and ABCA1 m RNA of DN group were significantly lower than that of normal group（P〈0.05）,and that of DN＋ApoA-I group was significantly higher than that of DN group（P〈0.05）.Conclusion ApoA-I/ABCA1 pathway was activated in vivo anti-DN key role in inflammation pathway and the mechanism by upregulating the TTP,thus contributing to the degradation of a variety of infl ammatory cytokines.