LL-37对COPD模型大鼠Th17/Treg平衡及炎症反应的调节作用  

Effect of human antimicrobial peptide LL-37 on Th17/Treg balance and inflammatory reaction in COPD rats

作　　者：李琳[1] 刘菊[1] 王爱利 肖方喜[1] 戴朝博[1] 李秀娟[1] Li Lin;Liu Ju;Wang Ai-li;Xiao Fang-xi;Dai Chao-bo;Li Xiu-juan(Wuhan No.1 Hospital,Wuhan 430022)

机构地区：[1]武汉市第一医院,武汉430022

出　　处：《中国抗生素杂志》2022年第10期1100-1104,I0001,共6页Chinese Journal of Antibiotics

基　　金：武汉市卫健委科研项目(No.WX20D25)。

摘　　要：目的观察人源抗菌肽LL-37对慢性阻塞性肺疾病(COPD)大鼠辅助性T细胞17(Th17)/调节性T细胞(Treg)平衡、炎症反应的影响,并探讨可能机制。方法40只Wistar大鼠随机分为正常组、COPD组、LL-37组、LL-37联合DAPT(Notch1/Jagged1信号通路抑制剂)组。正常组室温下正常喂养,COPD组、LL-37组、LL-37联合DAPT组采用烟熏法建立COPD模型。LL-37组大鼠经鼻滴入LL-37(10μg)50μL,LL-37联合DAPT组大鼠经鼻滴入总体积50μL的LL-37(10μg)+DAPT(10μg)。正常组、COPD组大鼠分别经鼻滴入等体积的生理盐水。检测外周血Th17、Treg细胞占比;检测肺泡灌洗液(BALF)中白介素-8(IL-8)、白三烯B4(LTB4)含量;HE染色检测气道重塑指标;Western Blot法检测肺组织Notch1、Jagged1、发状分裂相关增强子1(Hes1)蛋白表达量。结果与COPD组比较,LL-37组外周血Th17占比和Th17/Treg、BALF中IL-8、LTB4含量、管壁厚度/外径(MT%)及管壁面积/气管总面积(MA%)均降低,Treg占比升高(P<0.05);与LL-37组比较,LL-37联合DAPT组外周血Th17占比和Th17/Treg、BALF中IL-8、LTB4含量、MT%及MA%均升高,Treg占比降低(P<0.05)。与COPD组比较,LL-37组Notch1、Jagged1、Hes1蛋白表达量升高(P<0.05);与LL-37组比较,LL-37联合DAPT组Notch1、Jagged1、Hes1蛋白表达量降低(P<0.05)。结论人源抗菌肽LL-37可调节COPD大鼠外周血Th17/Treg失衡,抑制炎症反应及气道重塑,激活Notch1/Jagged1信号通路可能是其发挥治疗作用的机制之一。Objective To observe the effect of human antimicrobial peptide LL-37 on the balance of T helper 17(Th17)/regulatory T cells(Treg)and inflammatory response in chronic obstructive pulmonary disease(COPD)rats,and to explore the possible mechanism.Methods Forty Wistar rats were randomly divided into normal group,the COPD group,the LL-37 group,and the LL-37 combined with DAPT(Notch1/Jagged1 signaling pathway inhibitor)group.The normal group was fed normally at room temperature,and the COPD group,the LL-37 group,and the LL-37 combined with DAPT group were treated using the smoking method to establish the COPD model.Rats in the LL-37 group were injected with 50μL of LL-37(10μg)by nasal instillation,while rats in the LL-37 combined with DAPT group were injected with 50μL of LL-37(10μg)+DAPT(10μg)by nasal instillation.Rats in the normal group and the COPD group were instilled with an equal volume of normal saline through the nose.The proportion of Th17 and Treg cells in peripheral blood was detected;the contents of interleukin-8(IL-8)and leukotriene B4(LTB4)in bronchoalveolar lavage fluid(BALF)were detected;HE staining was used to detect airway remodeling indexes.Western blot was used to detect expressions of Notch1,Jagged1,and hairy division-related enhancer 1(Hes1)proteins in lung tissue.Results Compared with the COPD group,the proportion of Th17 in peripheral blood,Th17/Treg,IL-8,LTB4 content in BALF,wall thickness/outer diameter(MT%),and wall area/trachea total area(MA%)in the LL-37 group both decreased,and the proportion of Treg increased(P<0.05).Compared with the LL-37 group,peripheral blood Th17 proportion,Th17/Treg,IL-8,LTB4 content in BALF,MT%,and MA%increased in the LL-37 combined with DAPT group,and the proportion of Treg decreased(P<0.05).Compared with the COPD group,the protein expressions of Notch1,Jagged1,and Hes1 in the LL-37 group increased(P<0.05);compared with the LL-37 group,the protein expressions of Notch1,Jagged1,and Hes1 in the LL-37 combined with DAPT group decreased(P<0.05).Conclusion Human

关 键 词：慢性阻塞性肺疾病 人源抗菌肽LL-37 辅助性T细胞17 调节性T细胞 

分 类 号：R563[医药卫生—呼吸系统]