抑制CD18减轻脓毒症小鼠肠损伤的研究  

Study on inhibition of CD18 to alleviate intestinal injury in sepsis mice

作　　者：白镓玮 马承泰 严颜 吴淼[2] 杜贤进[1] BAI Jiawei;MA Chengtai;YAN Yan;WU Miao;DU Xianjin(Department of Critical Care Medicine,Renmin Hospital of Wuhan University,Wuhan,430060,China;Department of Emergency,Renmin Hospital of Wuhan University)

机构地区：[1]武汉大学人民医院重症医学科,武汉430060 [2]武汉大学人民医院急诊科

出　　处：《临床急诊杂志》2023年第3期143-148,共6页Journal of Clinical Emergency

基　　金：国家自然科学基金青年项目(No:82202409);湖北省自然科学基金项目(No:2022CFA089)。

摘　　要：目的:研究CD18在脓毒症肠损伤中的作用及机制。方法:将36只小鼠随机分为对照组、脓毒症组、抗CD18组,腹腔注射LPS建立脓毒症小鼠模型;抗CD18组先尾静脉注射CD18抗体,30 min后腹腔注射LPS;造模24 h后检测血清中β2整合素、D-乳酸、肝素结合蛋白(HBP)、肿瘤坏死因子-α(TNF-α)水平;检测小肠组织中炎症因子(IL-6、IL-10)、紧密连接蛋白(ZO-1、Claudin-1)、Rho信号通路蛋白(ROCK1、mDia1)的表达水平及RhoA活性;采用苏木精-伊红染色评估小肠病理损伤,透射电镜观察小肠组织超微结构改变。结果:(1)CD18抗体提高了脓毒症小鼠24 h存活率。(2)CD18抗体减轻了脓毒症小鼠小肠损伤(小肠病理损伤减轻、上皮间紧密连接破坏减轻、紧密连接蛋白表达增多),改善了肠道通透性(D-乳酸水平下降)。(3)CD18抗体抑制了Rho信号通路(RhoA活性下降、ROCK1和mDia1表达减少)。结论:抑制CD18可以减轻脓毒症肠损伤,改善肠道通透性;CD18可能是通过Rho信号通路参与了脓毒症的肠损伤。Objective: To study the role and mechanism of CD18 in sepsis intestinal injury. Methods: Thirty-six mice were randomly divided into control group, sepsis group and anti-CD18 group, and the sepsis mouse model was established by intraperitoneal injection of LPS. In the anti-CD18 group, CD18 antibody was injected into caudal vein at first, and LPS was injected intraperitoneally 30 min later. The serum levels of β2 integrin, HBP, D-lactate and TNF-α were detected 24 hours after modeling. Meanwhile, RhoA activity and the expression levels of inflammatory factors(IL-6, IL-10), tight junction proteins(ZO-1, Claudin-1), Rho signaling pathway proteins(ROCK1, mDia1) in small intestine were also detected. HE staining was used to evaluate the pathological damage of small intestine, and the ultrastructural changes of small intestine were observed by transmission electron microscopy. Results:(1)Anti-CD18 treatment increased the survival rate of sepsis mice for 24 h.(2)Anti-CD18 treatment attenuated intestinal pathological injury in sepsis mice, repaired tight junctions between epithelial cells(increase of tight junction proteins), and improved intestinal permeability(decrease of D-lactate level).(3)Anti-CD18 treatment inhibited the Rho signaling pathway(decrease of RhoA activity, decrease of ROCK1 and mDia1 expression). Conclusion: Inhibition of CD18 can alleviate intestinal damage and improve intestinal permeability in sepsis. CD18 may be involved in intestinal damage in sepsis through the Rho signaling pathway.

关 键 词：CD18 脓毒症 肠道通透性 紧密连接蛋白 Rho信号通路 

分 类 号：R631.2[医药卫生—外科学]