RhoF介导的Th17极化在急性胰腺炎发生中的作用及机制  

Role and mechanism of RhoF-mediated Th17 polarization in development of acute pancreatitis

作　　者：孙茹雪 朱梦莉 刘晶晶 陈飞 SUN Ruxue;ZHU Mengli;LIU Jingjing;CHEN Fei(Department of Emergency Medicine,Wuhan Integrated Tradi-tional Chinese and Western Medicine Hospital(Wuhan First Hospital),Wuhan 430030,China;不详)

机构地区：[1]武汉市中西医结合医院(武汉市第一医院)急诊医学科,武汉430030 [2]武汉市中西医结合医院(武汉市第一医院)心血管内科,武汉430030

出　　处：《实用医学杂志》2024年第10期1351-1356,共6页The Journal of Practical Medicine

基　　金：湖北省卫生健康科研基金项目(编号:20210836)。

摘　　要：目的探讨Rho相关GTP结合蛋白F(RhoF)介导的Th17极化在重度急性胰腺炎(SAP)发生中的作用及机制研究。方法将RhoF转基因小鼠随机分为3组:对照组(n=10)、SAP组(n=10)和SAP+Y-27632组(n=10)。另将WT小鼠随机分为3组:对照组(n=10)、SAP组(n=10)和SAP+Y-27632组(n=10)。除对照组外,其他组建立SAP模型。SAP+Y-27632组在模型建立后,通过尾静脉输注Y-27632。分离小鼠血液样本中的T细胞,用于RhoF、p-MYPT1蛋白检测和ROCK活性测定,并采用流式细胞仪分析产生IL-17的淋巴CD4+T细胞的百分比。结果与对照组相比,SAP组小鼠T细胞中RhoF、p-MYPT1表达量增加(P<0.01),并且RhoF的水平与p-MYPT1的水平密切相关(P<0.05)。与WT组相比,RhoF组小鼠T细胞的RhoF蛋白水平的表达增加约30%,并且CD4+T细胞自发产生IL-17的水平显著增加(P<0.01)。与WT小鼠相比,RhoF转基因小鼠胰腺损伤的组织学评分,T细胞的RhoF、p-MYPT1表达量,IL-17+T细胞数量和血清IL-17水平明显增加(P<0.05)。SAP+Y-27632组的组织学评分,T细胞的RhoF、p-MYPT1表达量,IL-17+T细胞数量和血清IL-17水平显著低于SAP组(P<0.05)。结论RhoF/ROCK信号通路介导的Th17细胞极化参与SAP的发病机制。Objective To investigate the role and mechanism of Rho-related GTP-binding protein F(RhoF)-mediated Th17 polarization in the development of severe acute pancreatitis(SAP).Methods RhoF transgenic mice were randomly divided into control group(n=10),SAP group(n=10)and SAP+Y-27632 group(n=10),and WT mice were randomly divided into control group(n=10),SAP group(n=10)and SAP+Y-27632 group(n=10).SAP models were established in all groups except the control group.The SAP+Y-27632 group was infused with Y-27632 via tail vein after model establishment.T cells in mouse blood samples were isolated for RhoF,p-MYPT1 protein detection and ROCK activity determination,and the percentage of lymphoid CD4+T cells producing IL-17 was analyzed by flow cytometry.Results The expression of RhoF and p-MYPT1 was increased in T cells in the SAP group compared with that in the control group(P<0.01),and the level of RhoF was closely correlated with that of p-MYPT1(P=0.018).The expression of RhoF protein level in T cells of mice in the RhoF group increased by approximately 30%compared to that in the WT group,and the level of spontaneous IL-17 production by CD4+T cells was significantly increased(P=0.003).Compared with WT mice,the histological score of pancreatic injury,the expression of RhoF and p-MYPT1 in T cells,the number of IL-17+T cells and serum IL-17 level in RhoF transgenic mice were significantly increased(P<0.05).The histological score,RhoF and p-MYPT1 expression of T cells,IL-17+T cell numbers and serum IL-17 level were significantly lower in the SAP+Y-27632 group than those in the SAP group(P<0.05).Conclusion RhoF/ROCK signaling pathway-mediated polarization of Th17 cells is involved in the pathogenesis of SAP.

关 键 词：Rho相关GTP结合蛋白F TH17细胞 重症急性胰腺炎 

分 类 号：R576.023[医药卫生—消化系统]