MAPK4敲除对内毒素诱导小鼠急性肺损伤的影响

Effects of MAPK4 deficiency on pathology of endotoxin-induced murine acute lung injury

目的:观察MAPK4敲除对内毒素诱导小鼠急性肺损伤的影响并探讨其意义。方法:利用脂多糖(LPS)腹腔注射野生型(WT)和MAPK4基因敲除(MAPK4 -/-)小鼠分别诱导小鼠急性肺损伤(ALI)模型;观察记录小鼠生存情况、小鼠体重变化和肺脏脏器指数变化;HE染色观察肺脏组织病理学变化情况;Real-time PCR检测肺脏组织中相关炎性因子mRNA表达水平变化;Western blot检测相关信号途径分子表达变化。结果:相比WT小鼠,生存分析结果显示MAPK4 -/-小鼠的生存时间明显增长;HE染色显示MAPK4 -/-小鼠肺脏组织炎性细胞浸润和肺泡间质增厚明显减少,病理性损伤明显减轻;Real-time PCR结果显示促炎因子IL-1β和TNF-α的mRNA表达水平明显降低,而抑炎因子TGF-β的mRNA表达水平明显增加( P <0.05);Western blot结果显示p-AKT和p-JNK的表达明显下调( P <0.01)。结论: MAPK4敲除可减轻小鼠ALI模型的肺部损伤,其机制可能与Akt和JNK信号途径传递变化相关,提示其在ALI的病理发生中有重要调控作用。

Objective: To detect the effects of MAPK4 deficiency on the pathology of murine acute lung injury(ALI),and preliminarily explore its significance. Methods: Murine ALI model was performed by intraperitoneal injection of Lipopolysaccharide(LPS)into wild-type(WT) and MAPK4 -/- mice respectively.Then,the survival results were observed.The pathologic injury of lung tissues was observed by HE staining.Moreover,the weight and lung weight index were recorded.The expressions of related cytokines in lung tissues were analyzed by Real-time PCR assay.Finally,the changes of related signaling pathways were measured by Western blot. Results: Compared with WT mice,the survival analysis showed that MAPK4 -/- mice owned longer survival time.The pathological damage in lung tissues was significantly alleviated in MAPK4 -/- mice.Real-time PCR analysis showed that pro-inflammatory cytokines IL-1β and TNF-α significantly decreased,at the same time,the expression of TGF-β obviously increased( P <0.05).Meanwhile,Western blot results showed that the expression levels of p-AKT and p-JNK decreased obviously in MAPK4 -/- mice( P <0.01). Conclusion: MAPK4 deficiency can ameliorate the pathology of murine ALI,which was related to the altered transduction of AKT and JNK pathway,indicating that it played an important role in the development of ALI.