PDX通过P38 MAPK通路促进脓毒症性ARDS抗菌肽cathelicidin表达

The expression of cathelicidin antimicrobial peptide increased by Protectin DX via P38 MAPK pathway in sepsis-induced ARDS

目的:探究PDX对脓毒症性ARDS抗菌肽cathelicidin(CAMP)的影响及其具体机制。方法:C57BL/6小鼠行盲肠结扎穿孔术建立脓毒症模型,分为:假手术组(Sham组)、脓毒症组(CLP组)、治疗组(CLP+PDX组)、抑制剂组(CLP+PDX+SB203580组)、溶剂对照组(CLP+PDX+DMSO组)、PDX组。采用HE染色观察肺组织损伤情况,进行肺损伤评分,菌落形成单位(CFU)检测细菌清除情况,qPCR检测肺组织CAMP基因表达情况,Westernblot检测肺组织CAMP蛋白表达以及P38MAPK、ERKMAPK通路激活情况。结果:与Sham组比,CLP组ERKMAPK通路无显著变化,P38MAPK通路受到抑制,CAMP表达显著升高(P<0.05);与CLP组相比,CLP+PDX组小鼠肺组织出血、炎性细胞浸润减轻,CFU显著降低,P38MAPK通路明显活化,且CLP+PDX组中CAMP表达进一步升高(P<0.05)。结论:PDX通过调控P38MAPK通路促进脓毒症性ARDSCAMP的表达。

Objective: To explore the effect of PDX on the expression of cathelicidin antimicrobial peptide in sepsis-induced ARDS and the possible signaling pathway. Methods: C57BL/6 mice underwent cecal ligation and puncture to establish the sepsis model. Mice were divided as: Sham group, CLP group, CLP+PDX group, CLP+PDX+SB203580 group, CLP+PDX+DMSO group and PDX group. HE staining was used to evaluate the lung injury situation, CFU was used to detect the colony forming situation. The expression of cathelicidin antimicrobial peptide gene in lung tissue was detected by qPCR. Western blot was used to detect the expression of CAMP and the activation of P38 MAPK and ERK MAPK pathway. Results: Compared with Sham group, ERK MAPK pathway showed no significant change in the CLP group, while P38 MAPK pathway was significantly inhibited (P<0.05), and CAMP expression increased distinctly (P<0.05);compared with the CLP group, mice in the CLP+PDX group had less hemorrhage, inflammtory cell infiltration in lung tissue, decreased obviously CFU while the activation of P38 MAPK and the expression of cathelicidin antimicrobial peptide increased significantly (P<0.05). Conclusion: PDX increased the expression of cathelicidin antimicrobial peptide via P38 MAPK pathway in sepsis-induced ARDS.