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

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摘要目的：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，Western blot检测肺组织CAMP蛋白表达以及P38 MAPK、ERK MAPK通路激活情况。结果：与Sham组比，CLP组ERK MAPK通路无显著变化，P38 MAPK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，P38 MAPK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P38 MAPK通路促进脓毒症性ARDS CAMP的表达。

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	谷丽君
	潘静怡
	Mohamed Ali Abdullahi
	金胜威

关键词 ：脓毒症, PDX, MAPK, 抗菌肽, cathelicidin

Abstract：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.

Key words： sepsis PDX MAPK antimicrobial peptide cathelicidin

收稿日期: 2019-02-10

基金资助:国家自然科学基金资助项目（81570076，81870065）。

通讯作者: 金胜威，主任医师，教授，Email：jsw@wmu.edu.cn。

作者简介: 谷丽君（1993-），女，浙江温州人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2019/V49/I7/469

[1] Alcayaga-Miranda F, Cuenca J, Khoury M. Antimicrobial activity of mesenchymal stem cells: current status and new perspectives of antimicrobial peptide-based therapies[J]. Front Immunol, 2017, 8: 339.
[2] Li Y, Xiang Q, Zhang Q, et al. Overview on the recent study of antimicrobial peptides: Origins, functions, relative mechanisms and application[J]. Peptides, 2012, 37(2): 207-215.
[3] Schauber J, Gallo R L. Antimicrobial peptides and the skin immune defense system[J]. J Allergy Clin Immunol, 2009, 124(3 Suppl 2): R13-18.
[4] BUCKLEY C D, GILROY D W, SERHAN C N, et al. The resolution of inflammation[J]. Nat Rev Immunol, 2013, 13(1): 59-66.
[5] Buckley C D, Gilroy D W, Serhan C N. Proresolving lipid mediators and mechanisms in the resolution of acute inflam-mation[J]. Immunity, 2014, 40(3): 315-327.
[6] SERHAN C N. Pro-resolving lipid mediators are leads for resolution physiology[J]. Nature, 2014, 510(7503): 92-101.
[7] Li H, Hao Y, Zhang H, et al. Posttreatment with Protectin DX ameliorates bleomycin-induced pulmonary fibrosis and lung dysfunction in mice[J]. Sci Rep, 2017, 7: 46754.
[8] Jung T W, Kim H C, Abd El-Aty A M, et al. Protectin DX ameliorates palmitate-or high-fat diet-induced insulin resistance and inflammation through an AMPK-PPARα-dependent pathway in mice[J]. Sci Rep, 2017, 7(1): 1397.
[9] Jung T W, Chung Y H, Kim H C, et al. Protectin DX attenuates LPS-induced inflammation and insulin resistance in adipocytes via AMPK-mediated suppression of the NFκB pathway[J]. Am J Physiol Endocrinol Metab, 2018, 315(4): E543-E551.
[10] Morishima I, Yamano Y, Inoue K, et al. Eicosanoids mediate induction of immune genes in the fat body of the silkworm, Bombyx mori[J]. FEBS Lett, 1997, 419(1): 83-86.
[11] Canny G, Levy O, Furuta G T, et al. Lipid mediator-induced expression of bactericidal/permeability-increasing protein (BPI) in human mucosal epithelia[J]. Proc Natl Acad Sci U S A, 2002, 99(6): 3902-3907.
[12] Campbell E L, MacManus C F, Kominsky D J,
et al. Resolvin E1-induced intestinal alkaline phosphatase promotes resolution of inflammation through LPS detoxifi-cation[J]. Proc Natl Acad Sci U S A, 2010, 107(32): 14298-14303.
[13] Dejager L, Pinheiro I, Dejonckheere E, et al. Cecal ligation and puncture: the gold standard model for polymicrobial sepsis?[J]. Trends Microbiol, 2011, 19(4): 198-208.
[14] Lyons M M, Raj N N, Chittams J L, et al. TAT-HSP70 attenuates experimental lung injury[J]. Shock, 2015, 43(6): 582-588.
[15] Perl M, Lomas-Neira J, Venet F, et al. Pathogenesis of indirect (secondary) acute lung injury[J]. Expert Rev Respir Med, 2011, 5(1): 115-126.
[16] Taranu I, Marin D E, Braicu C, et al. In vitro transcriptome response to a mixture of lactobacillistrains in intestinal porcine epithelial cell line[J]. Int J Mol Sci, 2018, 19(7). pii: E1923.
[17] JOSEPH S, YUEN A, SINGH V, et al. Mycobacterium tuberculosis Cpn60.2 (GroEL2) blocks macrophage apoptosis via interaction with mitochondrial mortalin[J]. Biol Open, 2017, 6(4): 481-488.
[18] Sun L, Wang W, Xiao W, et al. The roles of cathelicidin LL-37 in inflammatory bowel disease[J]. Inflamm Bowel Dis, 2016, 22(8): 1986-1991.
[19] Hwang H J, Jung T W, Kim J W, et al. Protectin DX prevents H2O2-mediated oxidative stress in vascular endothelial cells via an AMPK-dependent mechanism[J]. Cell Signal, 2019, 53: 14-21.
[20] XIA H, CHEN L, LIU H, et al. Protectin DX increases survival in a mouse model of sepsis by ameliorating inflammation and modulating macrophage phenotype[J]. Sci Rep, 2017, 7(1): 99.
[21] Kusaka S, Nishida A, Takahashi K, et al. Expression of human cathelicidin peptide LL-37 in inflammatory bowel disease[J]. Clin Exp Immunol, 2017, 191(1): 96-106.
[22] YANG R, YANG E, SHEN L, et al. IL-12+IL-18 cosignaling in human macrophages and lung epithelial cells activates cathelicidin and autophagy, inhibiting intracellular mycobacterial growth[J]. J Immunol, 2018, 200(7): 2405-2417.
[23] JIAO D, WONG C K, TSANG M S, et al. Activation of eosinophils interacting with bronchial epithelial cells by antimicrobial peptide LL-37: implications in allergic asthma[J]. Sci Rep, 2017, 7(1): 1848.
[24] Park K, Elias P M, Oda Y, et al. Regulation of cathelicidin antimicrobial peptide expression by an endoplasmic reticulum (ER) stress signaling, vitamin D receptor-independent pathway[J]. J Biol Chem, 2011, 286(39): 34121-34130.