P38MAPK信号通路在大鼠脓毒症致急性肺损伤中的作用及机制研究

The Role and Mechanism Research of P38MAPK Signal Pathway in Acute Lung Injury Induced by Sepsis of Rats

目的探讨P38MAPK信号通路在大鼠脓毒症致急性肺损伤中的作用及机制研究。方法 SD大鼠30只,随机分为假手术组、模型组、P38MAPK抑制剂组,每组10只。通过盲肠结扎穿刺术(CLP)建立大鼠脓毒症致急性肺损伤模型。予以P38MAPK抑制剂组尾静脉注射SB203580,注射后行CLP。造模后24h处死大鼠,观察大鼠肺病理组织学变化、肺湿/干比重值(W/D)、检测肺组织MDA、SOD含量、通过RT-qPCR和Western blot检测肺组织P38、P-P38的表达。结果模型组可见肺泡结构严重破坏,肺泡内可见出血、渗液,大量炎性细胞浸润。P38MAPK抑制剂组大鼠肺组织病理损伤较模型组轻(P<0.05)。模型组肺组织MDA较假手术组和P38MAPK抑制剂组高(P<0.05);模型组肺组织SOD较假手术组和P38MAPK抑制剂组低(P<0.05);模型组W/D较假手术组升高(P<0.05),P38MAPK抑制剂组W/D较模型组降低(P<0.05)。与假手术组相比,模型组肺P38 mRNA及蛋白表达水平升高(P<0.05),P-P38蛋白表达水平升高(P<0.05);与模型组相比,P38MAPK抑制剂组P38 mRNA及蛋白表达水平降低(P <0.05),P-P38蛋白表达水平降低(P <0.05)。结论抑制P38MAPK信号通路可以减轻大鼠脓毒症致急性肺损伤。

Objective To investigate the role and mechanism of P38MAPK signal pathway in acute lung injury induced by sepsis of rats.Methods 30 SD rats were randomly divided into sham operation group( SOG),model group( MG),and P38MAPK inhibitor group( IG),with 10 rats in each group.A model of acute lung injury induced by sepsis of rats was established by cecal puncture and ligation( CLP).SB203580 was injected into the tail vein of IG,and CLP was given after injection.Rats were sacrificed 24 h after modeling to observe the lung histopathological changes,lung wet/dry specific gravity value( W/D),detect lung tissue MDA,SOD content and detect lung tissue P38 and P-P38 by RT-qPCR and Western blot.Results MG showed severe destruction of the alveolar structure,bleeding and exudation in the alveoli,and a large number of inflammatory cell infiltration.The pathological damage of lung tissue in IG was lighter than that in MG( P<0.05).MDA of lung tissue in MG is higher than that in SOG and IG( P<0.05);SOD in MG is lower than that in SOG and IG( P< 0.05);W/D of MG was higher than that of SOG( P<0.05),and W/D of IG was lower than that of MG( P<0.05).Compared with SOG,the expression level of P38 mRNA and protein in the lungs of MG increased( P<0.05),and the expression level of P-P38 protein increased( P<0.05);compared with MG,P38 mRNA and protein expression levels of IG decreased( P<0.05),P-P38 protein expression levels decreased( P<0.05).Conclusion Inhibition of P38MAPK signaling pathway could reduce acute lung injury induced by sepsis of rats.