Hemin上调HO-1减轻急性肺损伤小鼠内质网应激及肺血管内皮功能障碍  

Effect of Hemin up-regulating HO-1 on pulmonary endoplasmic reticulum stress and vascular endothelial dysfunction in mice with acute lung injury

作　　者：赵爽[1] 唐凡人 唐旭毛 徐建华[1] ZHAO Shuang;TANG Fan-ren;TANG Xu-mao;XU Jian-hua(Department of Respiratory Medicine,Hechuan District People's Hospital,Chongqing 401520,China;Department of Respiratory and Critical Care Medicine,the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China)

机构地区：[1]重庆市合川区人民医院呼吸内科,重庆401520 [2]重庆医科大学附属第二医院呼吸与危重症医学科,重庆400010

出　　处：《临床肺科杂志》2020年第9期1305-1310,共6页Journal of Clinical Pulmonary Medicine

基　　金：重庆市卫健委办(2018-61)临床重点专科专项基金。

摘　　要：目的探讨血红素(Hemin)对脂多糖(LPS)所致急性肺损伤小鼠肺内质网应激标志蛋白和血管内皮的影响。方法30只雄性C57BL/6J小鼠分为对照组、模型组和治疗组。HE染色检查肺切片,BCA法检测支气管肺泡灌洗液(BALF)蛋白浓度,吉姆萨染色计数BALF总细胞和多形核白细胞(PMN),ELISA检测BALF中IL-1β、TNF-α,Western blot检测肺HO-1、GRP78、CHOP、VE-cadherin及β-catenin表达水平。结果与对照组相比,脂多糖组小鼠肺损伤明显,HO-1表达、湿/干比增高,BALF中细胞数、蛋白含量、IL-1β及TNF-α浓度明显升高,同时,GRP78、CHOP上调而VE-cadherin和β-catenin下调(P<0.05);血红素干预进一步上调了HO-1,减轻了小鼠肺损伤,降低了湿/干比、BALF细胞数、炎症因子水平和蛋白浓度,抑制了GRP78和CHOP的上调,并促进了VE-cadherin和β-catenin的表达(P<0.05)。结论血红素上调血红素加氧酶1,减轻急性肺损伤小鼠内质网应激及肺血管内皮功能障碍。Objective To investigate the effect of hemin on pulmonary endoplasmic reticulum stress and vascular endothelial dysfunction in mice with acute lung injury.Methods 30 healthy male C57BL/6 mice were randomly divided into the control group,the LPS group,and the H group with 10 mice in each group.Pathological changes of lung were evaluated by H&E staining.The IL-1βlevel and TNF-αlevel in bronchoalveolar lavage fluid(BALF)were determined by ELISA,and protein concentrations of BALFs were assessed by bicinchoninic acid(BCA)method.The total cell counts and polymorphonuclear neutrophil(PMN)counts in the BALF were analyzed by Giemsa staining.The protein levels of HO-1,CHOP,GRP78,VE-cadherin,andβ-catenin in lungs of each group were measured by Western blot.Results Compared with the control group,severe pathological lung injury was observed in the LPS group.The LPS group had increased total and PMNs counts,total protein levels,IL-1βand TNF-αlevels in BALF and lung injury score(P<0.05),while the HO-1,CHOP and GRP78 levels were higher,and VE-cadherin andβ-catenin levels were lower in lungs of the LPS group than those of the control group(P<0.05).Hemin attenuated the damage caused by LPS in the H group through heme oxygenase-1 induction(P<0.05).Conclusion Hemin can relieve pulmonary endoplasmic reticulum stress and vascular endothelial dysfunction by up-regulating heme oxygenase-1 induction in mice.

关 键 词：急性肺损伤 内质网应激 血红素 血红素加氧酶1 肺血管内皮 

分 类 号：R563[医药卫生—呼吸系统]