间充质干细胞外泌体通过抑制COX-2和NF-κB激活及p38 MAPK磷酸化缓解小鼠溃疡性结肠炎  

Mesenchymal stem cell exosomes alleviate ulcerative colitis in mice by inhibiting activation of COX-2 and NF-κB and phosphorylation of p38 MAPK

作　　者：刘继攀[1] 孙伟 宋默[1] 李凤丹[1] 赵学影[1] LIU Ji-Pan;SUN Wei;SONG Mo;LI Feng-Dan;ZHAO Xue-Ying(Harrison International Peace Hospital,Hengshui 053000,China)

机构地区：[1]哈励逊国际和平医院,衡水053000

出　　处：《中国免疫学杂志》2021年第14期1688-1692,1700,共6页Chinese Journal of Immunology

基　　金：河北省医学科学研究重点课题计划(20181496)。

摘　　要：目的:探究间充质干细胞(MSCs)外泌体对溃疡性结肠炎(UC)小鼠的影响及机制。方法:提取C57BL/6小鼠骨髓间充质干细胞(BMSCs)及其外泌体。30只C57BL/6小鼠随机分为control组、UC组、exosome组,UC组、exosome组小鼠饮用含3%DSS的饮用水造模,exosome组小鼠每3 d尾静脉注射1次10μg MSCs外泌体,control组和UC组注射等体积生理盐水,给药3周,记录小鼠疾病活动指数(DAI);ELISA检测血清炎症因子TNF-α、IL-6、IL-1β水平,记录小鼠黏膜损伤指数(CMDI),HE染色观察小鼠结肠组织病理变化,Western blot检测小鼠结肠组织中COX-2、NF-κB表达及p38 MAPK磷酸化水平。结果:与control组相比,UC组小鼠血清炎症因子TNF-α、IL-6、IL-1β水平、DAI、CMDI显著升高(P<0.001),结肠组织病变明显,结肠组织中COX-2、NF-κB表达及p38 MAPK磷酸化水平显著上调(P<0.001),与模型组相比,exosome组小鼠血清炎症因子TNF-α、IL-6、IL-1β水平、DAI、CMDI显著降低(P<0.001),结肠组织病变缓解,结肠组织中COX-2、NF-κB表达及p38 MAPK磷酸化水平显著下调(P<0.001)。结论:MSCs外泌体可显著缓解小鼠UC,其机制可能为抑制体内炎症反应、抑制COX-2、NF-κB表达及p38MAPK磷酸化。Objective:To investigate effect and mechanism of mesenchymal stem cell(MSCs)exosomes on mice with ulcerative colitis(UC).Methods:Bone marrow mesenchymal stem cells(BMSCs)and its exosomes were extracted from C57BL/6 mice.30 C57BL/6 mice were randomly divided into control group,UC group,and exosome group.UC group and exosome group mice drinking water contained 3%DSS for modeling,mice in exosome group were injected with 10μg MSCs exosomes every 3 d,and control and UC groups were injected with an equal volume of saline for 3 weeks.Disease activity index(DAI)was recorded.ELISA to detect serum inflammatory factors TNF-α,IL-6,IL-1βlevels,colonmucosa damage index(CMDI)of mice was recorded,HE staining to observe pathological changes of mouse colon tissue,Western blot to detect COX-2,NF-κB expressions and phosphorylation level of p38 MAPK in mouse colon tissue.Results:Compared with control group,serum inflammatory factors TNF-α,IL-6,IL-1βlevels,DAI,and CMDI of mice in UC group were significantly increased(P<0.001),colonic tissue lesions were obvious,COX-2,NF-κB expression and p38 MAPK phosphorylation level were significantly up-regulated(P<0.001).Compared with model group,exosome group serum inflammatory factors TNF-α,IL-6,IL-1βlevels,DAI,and CMDI were significantly decreased(P<0.001),colon tissue lesions were alleviated,expressions of COX-2,NF-κB and p38 MAPK phosphorylation in colon tissue were significantly decreased(P<0.001).Conclusion:MSCs exosomes can significantly alleviate UC in mice,whose mechanism may be inhibition of inflammatory response in vivo,inhibiting expressions of COX-2,NF-κB and phosphorylation of p38 MAPK.

关 键 词：溃疡性结肠炎 间充质干细胞外泌体 炎症 机制 

分 类 号：R364.4[医药卫生—病理学] R73-37[医药卫生—基础医学]