摘要
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。
Objectives： To investigate whether atorvastatin can induce heme oxygenase-l（ HO-1） expression 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（ Zn PPIX） group. A rat model of CI-AKI was established by intramuscular injection of gentamicin sulfate for 2 days and then intravascular injection of 76%meglumine diatrizoate. Atorvastatin group and Zn PPIX group were pretreated with atorvastatin/Zn PPIX before using meglumine diatrizoate. We detected changes in serum creatinine（ Scr） before and after model establishment,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 increased. 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 sig-nificantly（ P 0.05）,in Zn PPIX 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.
出处
《河北医学》
CAS
2018年第1期1-5,共5页
Hebei Medicine
基金
四川省卫生厅资助项目
(编号:090216)
