摘要
目的探讨罗格列酮(RSG)预处理减轻细菌脂多糖(LPS)所致小鼠急性肺损伤(ALI)进程中炎症和氧化应激的机制。方法将32只SPF级CD-1雄性小鼠随机分成对照组、RSG组、LPS 6 h组和RSG+LPS 6 h组。LPS 6 h组及RSG+LPS 6 h组小鼠经腹腔注射单剂量LPS(2 mg/kg);RSG组及RSG+LPS 6 h组小鼠于LPS注射前连续4 d,每天1次经口灌胃给予RSG(10 mg/kg)。LPS注射后6 h处死小鼠,留取血清和肺组织。用HE染色及病理积分评价肺组织病理学变化;用ELISA方法检测血清炎症趋化因子(KC)及促炎因子(TNF-α)表达水平;用Western blot方法检测肺组织NADPH氧化酶亚基(NOX-2、NOX-4)以及核因子-κB (NF-κB)信号通路(IκBα、p-IκBα、p-p65)蛋白表达水平。结果 RSG预处理减轻LPS所致小鼠ALI;RSG预处理减低LPS所致小鼠肺组织KC、TNF-α的升高,抑制小鼠肺组织NF-κB信号通路的激活;RSG预处理减低LPS诱导小鼠肺组织NOX-4蛋白的升高。结论 RSG预处理可能是通过抑制肺组织炎症和氧化应激反应减轻LPS所致小鼠ALI。
Objective To explore the mechanism of rosiglitazone(RSG) pretreatment in reducing inflammation and oxidative stress in the procession of acute lung injury(ALI) induced by bacterial lipopolysaccharide(LPS) in mice. Methods 32 SPF CD-1 male mice were randomly divided into Control group, RSG group, LPS 6 h group and RSG+LPS 6 h group. Mice in LPS group and RSG+LPS 6 h group were injected intraperitoneally with a single dose of LPS(2 mg/kg), while mice in RSG+LPS 6 h group and RSG group were given RSG(10 mg/kg) by oral gavage once a day for 4 days before LPS injection. The mice were killed 6 h after LPS injection, and the serum and lung tissue were collected. The pathological changes of lung tissue were evaluated by HE staining and pathological score, the levels of serum inflammation chemokine Keratinocyte-Derived Chemokine(KC) and proinflammatory factor Tumor Necrosis Factor-α(TNF-α) were detected by ELISA method, the protein expressions of NADPH oxidase subunits NOX-2,NOX-4 and nuclear factor-kappa B(NF-κB) signaling pathways(IκBα,p-IκBα,p-p65) in lung tissue were measured with Western blotting method. Results RSG pretreatment significantly attenuated LPS-induced ALI. RSG pretreatment obviously reduced the elevation of LPS-induced KC and TNF-α in lung tissue of mice, and the activation of LPS-induced NF-κB signaling pathway in lung tissue of mice was remarkedly alleviated. RSG pretreatment markedly inhibited the increase of NOX-4 protein in mice lung tissue induced by LPS. Conclusion RSG pretreatment may attenuate LPS-induced ALI in mice by inhibiting pulmonary inflammation and oxidative stress.
作者
丁章楠
博庆丽
费君
付林
陆友金
Ding Zhangnan;Bo Qingli;Fei Jun(Respiratory and Critically Ill Dept,The Second Hospital of Anhui Medical University,Hefei 230601;School of Public Health,Anhui Medical University,Hefei 230032)
出处
《安徽医科大学学报》
CAS
北大核心
2021年第2期282-286,共5页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金(编号:81803268)
安徽省自然科学基金(编号:1808085MH257)
安徽医科大学博士科研资助基金(编号:XJ201820)
安徽医科大学第二附属医院国家自然科学基金孵育计划(编号:2019GQFY06)。
关键词
罗格列酮
细菌脂多糖
急性肺损伤
炎症反应
氧化应激
rosiglitazone
lipopolysaccharide
acute lung injury
inflammatory response
oxidative stress reaction
