盐酸戊乙奎醚调控血管生成素2/血管内皮钙黏蛋白(Ang2/VE-cadherin)通路减轻脂多糖诱导的大鼠肺损伤  

Penehyclidine hydrochloride regulates angiopoietin 2/vascular endothelial cadherin(Ang2/VE-cadherin)pathway to alleviate LPS induced lung injury in rats

作　　者：杨逢永 房东东 张柄涵 孙燕洁 刘海峰 亓永杰 魏光晨 YANGFengyong;FANG Dongdong;ZHANG Binghan;SUN Yanjie;LIU Haifeng;QI Yongjil;WEI Guangchen(Jinan City People's Hospital EICU,Jinan Clinical Medicine Research Program for Respiratory Disease Medicine,Jinan 271100,China;Jinan Municipal Key Laboratory of Acute Lung Injury Medicine,Jinan Clinical Medicine Research Program for Respiratory Disease Medicine,Jinan 271100,China;Jinan Municipal Clinical Research Center of Critical Care Medicine,Jinan Clinical Medicine Research Program for Respiratory Disease Medicine,Jinan 271100,China)

机构地区：[1]济南市人民医院急诊科,山东济南271100 [2]济南市急性肺损伤医学重点实验室,山东济南271100 [3]济南市重症医学临床研究中心济南市呼吸病学临床研究中心,山东济南271100

出　　处：《细胞与分子免疫学杂志》2023年第8期708-713,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：山东医药卫生科技创新项目(2017WS137);济南市卫健委科研立项项目(2019-1-56)。

摘　　要：目的 探究盐酸戊乙奎醚(PHCD)对脓毒症大鼠血管内皮损伤的影响及作用机制。方法 雄性SD大鼠50只随机分为对照组、脂多糖(LPS)诱导大鼠脓毒症组,低、中、高剂量PHCD(0.3、 1.0、 3.0)mg/kg组,每组各10只。对照组尾静脉注射生理盐水,其余各组大鼠尾静脉注射10 mg/kg脂多糖(LPS)制备脓毒症大鼠模型,模型成功后大鼠尾静脉注射(0.3、 1.0、 3.0)mg/kg PHCD。测定各组大鼠肺组织湿/干质量比(W/D)、 ELISA检测支气管肺泡灌洗液(BALF)中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、 IL-6含量和大鼠血浆血管生成素2(Ang2)含量;HE染色观察肺组织病变情况;免疫组织化学染色观察右肺组织Ang2的表达,Western blot法检测肺组织Ang2、血管内皮钙黏蛋白(VE-cadherin)蛋白水平。结果 与对照组相比,模型组大鼠肺组织W/D以及BALF中IL-1β、 IL-6和TNF-α含量均显著增加,肺组织出现明显损伤,Ang2表达上调,VE-cadherin表达下调;与模型组相比,低、中、高剂量PHCD组大鼠肺组织W/D以及BALF中IL-1β、 IL-6和TNF-α含量均显著降低;肺组织损伤明显减轻,Ang2表达下调、 VE-cadherin表达上调。结论 PHCD可以通过调控Ang2/VE-cadherin通路,降低LPS诱导大鼠脓毒症肺部炎症,从而改善血管内皮损伤。Objective To explore the effect and mechanism of penehyclidine hydrochloride(PHCD)on vascular endothelial injury in septic rats.Methods Fifty male SD rats were randomly divided into control group,lipopolysaccharide(LPS)induced sepsis group(model group),low dose PHCD(0.3 mg/kg)group,medium dose PHCD(1.0 mg/kg)group and high dose PHCD(3.0 mg/kg)groups,ten mice for each group.Normal saline was injected into the tail vein of the control group,and 10 mg/kg lipopolysaccharide(LPS)was injected into the tail vein of the rats in other groups to prepare the sepsis rat models.After the models were successfully established,low,medium and high doses(0.3,1.0,3.0 mg/kg)of PHCD solution were injected into the tail vein of the rats of corresponding groups.Wet/dry mass ratio(W/D)of lung tissue of rats in each group was measured,and ELISA was used to assay interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),IL-6 content and rat plasma angiopoietin 2(Ang2)content in bronchoalveolar lavage fluid(BALF).HE staining was used to observe the pathological changes of lung tissues.Immunohistochemical staining was used to observe the expression of Ang2 in the right lung tissues.Western blot analysis was performed to detect Ang2 and vascular endothelial cadherin(VE-cadherin)protein in lungtissues.ResultsCompared with the control group,the W/D ratio of the lung tissues of rats in the model group and the contents of IL-1β,IL-6 and TNF-αin BALF were significantly increased;the lung tissues showed obvious pathological damage,with up-regulation of Ang2 expression and down-regulation of VE-Cadherin expression.Compared with the model group,the W/D ratio of the lung tissues of rats in three PHCD treatment groups and the contents of IL-1β,IL-6 and TNF-αin BALF were significantly reduced;the pathological damage of lung tissue was significantly reduced,with down-regulation of Ang2 expression and up-regulation of VE-cadherin expression.Conclusion PHCDcan reduce LPS-induced lung inflammation in rats with sepsis by regulating the Ang2/VE-Cadherin p

关 键 词：盐酸戊乙奎醚(PHCD) 脓毒症 血管内皮损伤 血管生成素2(Ang2) 血管内皮钙黏蛋白(VE-cadherin) 

分 类 号：R364.5[医药卫生—病理学] R563.2[医药卫生—基础医学] R392.11R965