摘要
目的探讨罗格列酮(rosiglitazone,RSG)抑制细菌脂多糖(lipopolysaccharide,LPS)所致急性肾损伤过程中氧化应激的机制。方法 48只雄性CD-1小鼠随机分成对照组、RSG组、LPS 6 h组、LPS 24 h组、RSG+LPS 6 h组和RSG+LPS 24 h组共6组。LPS组小鼠经腹腔注射给予单剂量LPS(2 mg/kg);RSG+LPS组于LPS注射前经口灌胃给予RSG(10 mg/kg),每天1次,连续4 d。LPS注射后6 h和24 h取小鼠血清和肾脏组织。一侧肾脏用于苏木精-伊红染色法(hematoxylin-eosin staining,简称HE染色法)并观察肾脏病理学损伤;用全自动生化分析仪检测血清肌酐和尿素氮反映肾功能;用生化方法检测肾脏还原型谷胱甘肽(glutathione,GSH)和丙二醛(malondialdehyde,MDA)水平;用real time RT-PCR检测肾脏氧化应激相关基因(P47phox,Sod-1,Sod-2,Sod-3)表达水平;用蛋白质印迹(western blot,简称WB)法检测肾脏NADPH氧化酶亚基NOX-2和NOX-4蛋白水平。结果 RSG预处理明显减轻LPS所致肾小管破坏和肾功能损害,抑制LPS所致肾脏炎性细胞浸润;RSG预处理抑制LPS所致肾脏MDA水平升高,LPS暴露下调了肾脏GSH水平,RSG预处理有改善LPS诱发GSH耗竭的趋势,但无统计学意义;RSG阻断LPS上调肾脏P47phox mRNA表达水平;RSG预处理抑制LPS诱导肾脏NOX-2和NOX-4蛋白表达水平升高。结论 RSG预处理减轻LPS诱发肾脏氧化应激反应。
Objective To investigate the effects of pretreatment with rosiglitazone(RSG) on oxidative stress in lipopolysaccharide(LPS)-induced acute kidney injury(AKI). Methods Forty-eight male ICR mice were divided into six groups: Control group, RSG group, LPS 6 h group,LPS 24 h group,RSG+LPS 6 h group, and RSG+LPS 24 h group. In the LPS and LPS+RSG groups, mice were intraperitoneal injected with LPS(2 mg/kg). In the RSG and RSG+LPS groups, mice were administered with RSG(10 mg/kg) by gavage four consecutive days before LPS injection. All mice were sacrificed at 6 h and 24 h after LPS injection. Some kidneys were collected for HE staining. Renal GSH and MDA were detected using biochemical method. Renal oxidant stress related genes were analyzed through real time RT-PCR. Renal NADPH oxidase-2 and NOX-4 were measured by Western blot. Serum was acquired for renal function. Results LPS-induced AKI, as determined renal pathological damage,renal function injury and inflammatory cell infiltration, were attenuated in RSG-pretreated mice. Although it did not affect renal GSH level, RSG pretreatment evidently inhibited the elevation of renal MDA content. Mechanistically, RSG pretreatment distinctly repressed LPS-induced upregulation of P47phox mRNA and nicotinamide adenine dinucleotide phosphate(NADPH) oxidase(NOX)-2 and NOX-4 in the kidney. Conclusion RSG pretreatment attenuates renal oxidative stress in LPS-induced acute kidney injury partially through inhibiting upregulation of NADPH oxidase.
作者
魏啸
付林
博庆丽
徐德祥
吴永贵
WEI Xiao;FU Lin;BO Qing-li;XU De-xiang;WU Yong-gui(Center of Blood Purification,Department of Nephrology,the First Affiliated Hospital of Anhui Medical University,Hefei 230032,China;Department of Toxicology,School of Public Health,Anhui Medical University,Hefei 230032,China;Department of Nephrology,the First Affiliated Hospital of Anhui Medical University,Hefei 230032,China)
出处
《中华疾病控制杂志》
CAS
CSCD
北大核心
2020年第5期597-601,共5页
Chinese Journal of Disease Control & Prevention
基金
国家自然科学基金(81803268)
安徽省自然科学基金(1808085MH257)
安徽医科大学博士科研资助基金(XJ201820)。
