To explore the protective effect of sodium channels antagonists HOE642 on lung ischemia 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 pathological changes were observed under optical microscope. The inflammatory cytokines including IL-6 and TNF-α were examined by ELISA. The intracellular calcium fluorescence intensity was examined and observed under fluorescence microscope, and the protein expression of p38MAPK was detected by Western blot. Results: Lung water content in the HOE group was lower than that in the I/R group, but higher than that in the SHAM group (both P<0.05). Lung interstitial edema, hemorrhage, lung tissue inflammatory 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, but higher than those in the SHAM group (both P<0.05). Intracellular calcium fluorescence intensity in 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 lower than 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 of the p38MAPK signaling pathway, resulting in reduction of intracellular calcium ion concentration and calcium overload, and decrease of inflammatory response.
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。.