p38 丝裂原活化蛋白激酶信号通路在阻滞剂HOE642对肺缺血再灌注保护中的作用

目的：探讨钠氢通道阻断剂HOE642对肺缺血再灌注损伤的保护作用，以及其保护作用与p38丝裂原活化蛋白激酶(p38 mitogen activated protein kinase，p38MAPK)通路的关系。方法：选取野生小鼠36只，随机分为假手术组(SHAM组)、肺缺血再灌注组(I/R组)和肺缺血再灌注+HOE642组(HOE组)，建立肺缺血再灌注损伤模型。测定肺组织含水量；光镜下观察肺组织病理学变化；ELISA检测炎症反应水平(IL-6，TNF-α)；测定肺组织细胞内钙离子荧光强度；测定肺组织p38MAPK的蛋白表达。结果：HOE组肺组织含水量低于I/R组，但高于SHAM组(均P<0.05)；HOE组肺组织间质水肿、出血、炎症细胞浸润的情况比I/R组明显减轻，但比SHAM组严重(均P<0.05)；HOE组肺组织IL-6和TNF-α水平低于I/R组，但高于SHAM组(均P<0.05)；HOE组细胞内钙离子荧光强度低于I/R组，但高于SHAM组(均P<0.05)；HOE组肺组织p38MAPK的蛋白表达量低于I/R组，但高于SHAM组(均P<0.05)。结论：HOE642可能通过调节p38MAPK信号通路，降低细胞内的钙离子浓度和钙超载，减轻炎症反应而发挥肺保护作用。

Role of p38 mitogen activated protein kinase signaling pathwayin lung ischemia-reperfusion protection offered by HOE642

Objective: To explore the protective effect of sodium channels antagonists HOE642 on lungischemia reperfusion and the role of the p38 mitogen activated protein kinase (p38MAPK)signaling pathway in this process.Methods: A total of 36 mice were randomly divided into a sham operation group (SHAM group),a lung ischemia reperfusion group (I/R group) and a lung ischemia reperfusion+HOE642 group(HOE group). The water content was detected by electronic scales, and the lung tissue pathologicalchanges were observed under optical microscope. The inflammatory cytokines including IL-6 andTNF-α were examined by ELISA. The intracellular calcium fluorescence intensity was examinedand observed under fluorescence microscope, and the protein expression of p38MAPK wasdetected by Western blot.Results: Lung water content in the HOE group was lower than that in the I/R group, but higherthan that in the SHAM group (both P<0.05). Lung interstitial edema, hemorrhage, lung tissueinflammatory cells infiltration were significantly alleviated in the HOE group than those in the I/R group,while the injury in the HOE group was aggravated than those in the SHAM group (both P<0.05).The IL-6 and TNF-α in lung tissues in the HOE group were lower than those in the I/R group, buthigher than those in the SHAM group (both P<0.05). Intracellular calcium fluorescence intensityin the HOE group was lower than that in the I/R group, but higher than that in the SHAM group(both P<0.05). The protein expression of p38MAPK in lung tissues in the HOE group was lowerthan that in the I/R group, but higher than that in the SHAM group (both P<0.05).Conclusion: HOE642 may exert protective effect on pulmonary I/R injury through regulation ofthe p38MAPK signaling pathway, resulting in reduction of intracellular calcium ion concentrationand calcium overload, and decrease of inflammatory response.