不同他汀类药物对大鼠造影剂诱导的急性肾损伤的影响比较:组织病理学和生化研究结果
Comparison of Effects of Different Statins on Contrast-Induced Acute Kidney Injury in Rats: Histopathological and Biochemical Findings.
作者信息
Wang Xiao-Lei, Zhang Tuo, Hu Liu-Hua, Sun Shi-Qun, Zhang Wei-Feng, Sun Zhe, Shen Ling-Hong, He Ben
机构信息
Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
出版信息
Oxid Med Cell Longev. 2017;2017:6282486. doi: 10.1155/2017/6282486. Epub 2017 Jan 24.
Statins are a promising new strategy to prevent contrast-induced acute kidney injury (CI-AKI). In this study we compared the ameliorative effect of different statins in a rat model of CI-AKI. Sprague-Dawley rats were divided into five groups: control group; CI-AKI group; CI-AKI + rosuvastatin group (10 mg/kg/day); CI-AKI + simvastatin group (80 mg/kg/day); and CI-AKI + atorvastatin group (20 mg/kg/day). CI-AKI was induced by dehydration for 72 hours, followed by furosemide intramuscular injection 20 minutes before low-osmolar contrast media (CM) intravenous injection. Statins were administered by oral gavage once daily for 3 consecutive days before CM injection and once 4 hours after CM injection. Rats were sacrificed 24 hours after CM injection, and renal function, kidney histopathology, nitric oxide (NO) metabolites, and markers of oxidative stress, inflammation, and apoptosis were evaluated. The results showed that atorvastatin and rosuvastatin but not simvastatin ameliorated CM-induced serum creatinine elevation and histopathological alterations. Atorvastatin and rosuvastatin showed similar effectiveness against CM-induced oxidative stress, but simvastatin was less effective. Atorvastatin was most effective against NO system dysfunction and cell apoptosis, whereas rosuvastatin was most effective against inflammation. Our findings indicate that statins exhibit differential effects in preventing CI-AKI when given at equivalent lipid-lowering doses.
他汀类药物是预防造影剂诱导的急性肾损伤(CI-AKI)的一种有前景的新策略。在本研究中,我们比较了不同他汀类药物在CI-AKI大鼠模型中的改善作用。将Sprague-Dawley大鼠分为五组:对照组;CI-AKI组;CI-AKI + 瑞舒伐他汀组(10毫克/千克/天);CI-AKI + 辛伐他汀组(80毫克/千克/天);以及CI-AKI + 阿托伐他汀组(20毫克/千克/天)。通过脱水72小时诱导CI-AKI,然后在低渗造影剂(CM)静脉注射前20分钟肌肉注射速尿。在CM注射前连续3天每天经口灌胃给予他汀类药物,在CM注射后4小时给予一次。在CM注射后24小时处死大鼠,并评估肾功能、肾脏组织病理学、一氧化氮(NO)代谢产物以及氧化应激、炎症和细胞凋亡标志物。结果表明,阿托伐他汀和瑞舒伐他汀可改善CM诱导的血清肌酐升高和组织病理学改变,而辛伐他汀则无此作用。阿托伐他汀和瑞舒伐他汀对CM诱导的氧化应激显示出相似的效果,但辛伐他汀效果较差。阿托伐他汀对NO系统功能障碍和细胞凋亡最有效,而瑞舒伐他汀对炎症最有效。我们的研究结果表明,给予等效降脂剂量时,他汀类药物在预防CI-AKI方面表现出不同的作用。