摘要
目的探讨激活PPARγ对脂多糖(lipopolysaccharide,LPS)诱导的小鼠急性肺损伤的保护作用及可能的机制。方法6-8周雄性BALB/c小鼠15只随机分3组,对照组(Con组):气管内滴注无菌PBS 60μl作用24 h;LPS模型组(LPS组):气管内滴注1 mg/ml LPS 60μl作用24 h;罗格列酮治疗组(Rosi+LPS组),滴注LPS前24 h和0.5 h给予PPARγ激动剂罗格列酮(20 mg/kg)灌胃,气管内滴注LPS 60μl造模24 h。观察各组小鼠肺组织病理学变化,支气管肺泡灌洗液(BALF)中炎症细胞总数及中性粒细胞变化,ELISA法检测BALF中炎症细胞因子IL-6的浓度,免疫印迹法检测肺组织中HO-1蛋白表达变化。结果与对照组相比,LPS模型组病理学显示大量的炎性细胞浸润,肺组织结构明显被破坏,支气管肺泡灌洗液中细胞总数和中性粒细胞数明显增高(P<0.01),BALF中IL-6显著升高(P<0.01),肺组织内HO-1蛋白表达较对照组没有明显差异(P>0.05)。与LPS模型组相比,罗格列酮治疗组小鼠肺组织结构破坏减轻,炎症细胞浸润减少,支气管肺泡灌洗液中IL-6浓度下降(P<0.01),肺组织内HO-1蛋白表达显著增加(P<0.01)。结论激活PPARγ可减轻LPS诱导急性肺损伤,这种保护作用可能与HO-1的上调有关。
Objective To investigate the protective effect of activation of PPAR-γagainst lipopolysaccharide(LPS)-induced acute lung injury in mice and its possible mechanism.Methods Fifteen male BALB/c mice(6-8 weeks)were randomized into three groups.The mice in control group were intratracheally given sterile PBS(60μl).The mice in LPS model group were instilled intratracheally with 60μl of LPS(1 mg/ml)for 24 h.The mice in rosiglitazone group were treated with rosiglitazone(30 mg/kg)orally at 24 h and 0.5 h before instilled intratracheally with LPS(1 mg/ml,60μl)for 24 h.After administration of LPS for 24 h,the histopathological changes of lung tissue,the numbers of total cells and neutrophils in bronchoalveolar lavage fluid(BALF)in each group were observed.The concentration of IL-6 in BALF was measured by ELISA.The expression of HO-1 in lung tissue was detected by Western blot.Results Compared with control group,the pathology in LPS model group showed a large number of inflammatory cells infiltration and lung tissue structure was significantly damaged.Compared with control group,the total number of cells,neutrophils and IL-6 in bronchoalveolar lavage fluid increased significantly(P<0.01).Compared with control group,the expression of HO-1 protein in LPS model group showed no significant change(P>0.05).Compared with LPS model group,the mice showed less damage to lung tissue structure,less infiltration of inflammatory cells(P<0.01),and lower concentration of IL-6 in bronchoalveolar lavage fluid in rosiglitazone group(P<0.01).Compared with LPS model group,the expression of HO-1 protein in rosiglitazone group increased significantly(P<0.01).Conclusion The activation of PPARγcan reduce LPS-induced acute lung injury,which may be related to up-regulation of expression of HO-1.
作者
王贵佐
陈芬芬
张叶钦
苗毅
刘璐
尚文丽
WANG Guizuo;CHEN Fenfen;ZHANG Yeqin;MIAO Yi;LIU Lu;SHANG Wenli(Department of Respiratory and Critical Care Medicine,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;Department of Cadre Healthcare Office,Second Affiliated Hospital of Xi’an Jiaotong University)
出处
《山西医科大学学报》
CAS
2019年第12期1694-1697,共4页
Journal of Shanxi Medical University
基金
陕西省中医药管理局课题资助项目(2019-ZZ-JC037)
陕西省自然科学基金资助项目(2018JM7078)
