线粒体融合蛋白2在急性呼吸窘迫综合征大鼠肺纤维化中的表达  

Expression of mitochondrial fusion protein 2 in pulmonary fibrosis in rats with acute respiratory distress syndrome

作　　者：安宁[1] 许涛 周贤 刘涛 戴仲 许美霞 AN Ning;XU Tao;ZHOU Xian;LIU Tao;DAI Zhong;XU Meixia(Institute of Anesthesia and Critical Care Medicine,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,Hubei,China;Dept.of Intensive Care Unit,Wuhan Fourth Hospital,Wuhan 430034,Hubei,China)

机构地区：[1]华中科技大学同济医学院附属协和医院麻醉与危重病研究所,湖北武汉430022 [2]武汉市第四医院重症医学科,湖北武汉430034

出　　处：《武汉大学学报（医学版）》2023年第11期1311-1315,共5页Medical Journal of Wuhan University

基　　金：湖北省卫生健康委员会基金项目(编号:WJ2023M030);湖北省卫生健康委员会联合基金项目(编号:WJ2019H324);湖北省自然科学基金项目(编号:2022CFB423);武汉市卫生健康委员会科研基金(编号:WX19A09)。

摘　　要：目的:探讨线粒体融合蛋白2(Mfn2)在脂多糖(LPS)致急性呼吸窘迫综合征(ARDS)大鼠肺纤维化过程中的表达规律。方法:48只雄性SD大鼠随机分为Control组、LPS组,每组根据给药后的时间点(1 d、3 d、7 d、14 d)分为4个亚组(T1、T3、T7、T14)。取大鼠肺组织,HE染色光镜下观察肺组织病理变化,并检测肺组织羟脯氨酸(HYP)含量;肺组织切片常规免疫组化染色,检测肺组织中Mfn2的表达;Western Blot及Real time-PCR分别检测Mfn2蛋白、mRNA的表达情况。结果:HE染色显微镜下观察可见LPS组大鼠肺组织出现肺间质纤维化,肺泡结构紊乱;肺组织HYP含量测定显示,LPS组造模后3 d、7 d、14 d HYP含量与Control组比较明显增加(均P<0.05)。免疫组化显示,Control组肺组织中存在Mfn2表达,大鼠气管内滴注LPS 3 d后肺组织Mfn2表达即开始减少;Western Blot及RTPCR检测结果显示,与Control组比较,LPS组造模后3 d、7 d、14 d肺组织中Mfn2蛋白及基因表达均明显下调(均P<0.05)。结论:气管内滴注LPS可诱导大鼠出现急性肺损伤及肺纤维化,在损伤的肺组织中Mfn2表达明显减少,提示Mfn2与内毒素所致大鼠急性肺损伤及肺纤维化密切相关。Objective:To investigate the expression of mitochondrial fusion protein 2(Mfn2)in lipopolysac⁃charide(LPS)⁃induced pulmonary fibrosis in rats with acute respiratory distress syndrome(ARDS).Method:A total of forty⁃eight male SD rats were divided into the control group and LPS group,and each group was divided into four subgroups(T1,T3,T7,and T14)according to the time points of treatment(1,3,7,and 14 day(s)after administration).The lung tissue was collected and stained with HE.The pathological changes of lung tissue were observed,and the content of hydroxyproline(HYP)in the lung tissue was detected.Routine immunohistochemical staining of lung tissue sections was used to detect the expression of Mfn2 in lung tissue;Western Blot and real time⁃PCR were adopt⁃ed to detect the protein and mRNA expression of Mfn2 in lung tissue.Results:Pathological results showed that pulmonary interstitial fibrosis was formed in the lung,and the alveolar structure was dis⁃ordered.The HYP contents of the LPS group were increased at the time⁃points of T3,T7,and T14(all P<0.05).Immunohistochemistry showed that the expression of Mfn2 in the lung tissue of the rats began to decrease after T3.The results of Western Blot and RT⁃PCR showed that compared with those of the control group,the Mfn2 protein and gene expression in lung tissue of the LPS group were significantly down⁃regulated at T3,T7,and T14(all P<0.05).Conclusion:Intratracheal instil⁃lation of LPS can induce acute lung injury and pulmonary fibrosis in rats,and the expression of Mfn2 in injured lung tissue is significantly reduced,suggesting that Mfn2 is closely related to LPS⁃induced acute lung injury and pulmonary fibrosis in rats.

关 键 词：线粒体融合蛋白2 脂多糖 急性呼吸窘迫综合征 肺纤维化 

分 类 号：R563.9[医药卫生—呼吸系统]