阿托伐他汀预诱导HO-1表达对泛影葡胺致大鼠急性肾损伤模型保护性作用研究

摘要

Objectives:To investigate whether atorvastatin can induce heme oxygenase-l ( HO-1) ex-pression in rat kidneys to prevent contrast-induced acute kidney injury( CI-AKI) and its related mechanisms. Methods:48 healthy Sprague-Dawley male rats were randomly divided into the blank control group, model group , atorvastatin group and zinc protoporphyrin IX(ZnPPIX) group. A rat model of CI-AKI was estab-lished by intramuscular injection of gentamicin sulfate for 2 days and then intravascular injection of 76％meglumine diatrizoate. Atorvastatin group and ZnPPIX group were pretreated with atorvastatin/ZnPPIX before using meglumine diatrizoate. We detected changes in serum creatinine ( Scr) before and after model establish-ment, measured the interleukin-6 ( IL-6 ) , monocyte chemotactic protein 1 ( MCP-1 ) , malondialdehyde ( MDA) and total antioxidant capacity ( T-AOC) as well as the protein expression of HO-1, Bax, Bcl-2 in the renal tissue, and analyzed the renal cell apoptosis index ( AI ) . Results:After contrast agent injection, compared with the control group,the SCr of the other three groups were significantly increased and reached the CI-AKI standard, Meanwhile, the inflammatory and oxidative stress markers and AI were also significantly in-creased. Compared with the model group, in atorvastatin group, the expression of HO-1 protein in renal tissue increased significantly, while the level of inflammation and oxidative stress and both AI and SCr decreased significantly ( P<0.05) ,in ZnPPIX group, the expression of HO-1 protein in renal tissue also increased, but the level of inflammation and oxidative stress and both AI and SCr increased significantly( P<0.05) . Conclusion:Atorvastatin can induce expression of HO-1 protein in rat kidney throuh which inhibit the renal inflammation and oxidative stress and cell apoptosis, thereby protecting against CI-AKI.%目的:探讨阿托伐他汀能否通过预诱导大鼠肾内血红素氧合酶-l(HO-1)表达防止泛影葡胺致大鼠急性肾损伤(CI-AKI)及其相关机制.方法:健康雄性SD大鼠48只随机均分为4组:对照组、模型组、阿托伐他汀组、锌原卟啉(ZnPPIX)组,采用先肌注2d庆大霉素后再血管内注射76％复方泛影葡胺的方法复制CI-AKI模型,阿托伐他汀组、锌原卟啉(ZnPPIX)组在用泛影葡胺前还先给阿托伐他汀/ZnPPIX预处理.检测血肌酐(SCr)变化及肾组织中HO-1、IL-6、MCP-1、Bax、Bcl-2蛋白表达量及总抗氧化能力(TAOC)、MDA含量和细胞凋亡指数(AI).结果:与对照组相比,其余三组应用对比剂后SCr均明显升高并达到CI-AKI标准,且各项炎症与氧化应激指标和AI也都明显升高.与模型组比较,阿托伐他汀组肾内HO-1蛋白表达量明显升高,炎症与氧化应激水平明显降低,AI及SCr均显著降低(P均<0.05);ZnPPIX组HO-1蛋白表达量也升高,但炎症与氧化应激水平却反而升高,AI及SCr也明显升高(P均<0.05).结论:阿托伐他汀可诱导大鼠肾内HO-1蛋白表达并通过后者抑制炎症、氧化应激和细胞凋亡,从而发挥抗对比剂急性肾损伤效果.