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作 者:苑萌 卢晶 韩宝华[1] 张志斌[1] 王佳[1] YUAN Meng;LU Jing;HAN Baohua;ZHANG Zhibin;WANG Jia(Department of Emergency,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei,075000,China)
机构地区:[1]河北北方学院附属第一医院急诊科,河北省张家口市075000
出 处:《医学分子生物学杂志》2021年第1期32-39,共8页Journal of Medical Molecular Biology
基 金:河北省2020年度医学科学研究课题计划(No.20200521)。
摘 要:目的探究麻黄水提物(ephedra water extract,EWE)对肺炎克雷伯菌所致重症肺炎幼龄大鼠细胞因子、间质纤维化及NF-κB活化的影响方法采用肺炎克雷伯菌标准株菌液构建重症肺炎模型,EWE灌胃(100、200、400 mg/kg)治疗,10 d后检测各组幼鼠肺功能,以及外周血中炎性细胞因子白介素名(IL-6)、IL-10、诱导型一氧化氮合酶(iNOS)水平;取双侧肺组织测量肺评分及湿干重比,并制成切片进行HE、TUNEL、Masson染色观察肺组织病理、凋亡及间质纤维化情况,Western印迹法检测肺组织中凋亡蛋白Caspase-3、Caspase-9和纤维化相关蛋白α-滑肌肌动蛋白(α-SMA)、纤维连接蛋白(fibronectin),层黏连蛋白(laminin)、P65、p-P65表达水平。结果不同剂量EWE能够改善重症肺炎大鼠肺功能指标、肺组织病理损伤,降低IL-6、iNOS水平,提高IL-10水平,抑制重症肺炎引起的肺组织细胞凋亡及Caspase-3、Caspasf-9蛋白表达,缓解肺间质纤维化下调肺组织中纤维化相关蛋白α-SMA、Fibronectin、Laminin表达,抑制NF-κB信号通路关键蛋白磷酸化。结论EWE可能通过抑制NF-κB信号通路活化改善肺炎克雷伯菌所致重症肺炎引起的肺组织炎性反应来保护肺功能以及间质纤维化。Objective To explore tlie effects of ephedra water extract(EWE)on cytokines,interstitial fibrosis and NP-κB activation in immature rats with severe pneumonia caused by Klebsiella pneumoniae.Methods The severe pneumonia models were constmcted in immature rats by the liquid of the standard sirdlnKlebsiella pneumoniae.Animals were intragastrically given EWE(100,200,400 mg/kg).After 10days,pulmonary function,levels of inflammatory cytokines[interleukin-6(IL-6),IL-10]and inducible nilric oxide synthase(iNOS)in the peripheral blood were detected.The bilateral pulmonary tissues were collected to detect the pulmonary score and wet-to-dry weight.The pathology,apoptosis and interstitial fibrosis of pulmonary tissues were observed by HE,TUNEL and Masson staining.The expression levels of apoptosis-related proteins(Caspase-3,Caspase-9)and fibrosis-related proteins[α-smooth muscle actin(α-SMA),fibronectin(FN),laminin(LN)]in pulmonary tissues were detected by Western blotting.Results Different doses of EWE could improve pulmonary function indexes and pathological damage of pulmonary tissues in rats with severe pneumonia.They could decrease IL-6 and iNOS levels,increase IL-10 level,inhibit apoptosis in pulmonary tissues and expression of Caspase-3 and Caspase-9 proteins,alleviate pulmonary interstitial fibrosis,down-regulate the expression of fibrosis-related proteins(α-SMA,FN,LN)in pulmonary tissues,and suppress the phosphorylation of key proteins in NF-κB signaling pathway.Conclusion EWE may improve pulmonary function and interstitial fibrosis by inhibiting the activation of NF-κB signaling pathway and alleviating the inflammatoiy response of pulmonary tissues in severe pneumonia caused hyKlebsiella pneumoniae.
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