富马酸氯马斯汀减轻小鼠肠缺血/再灌注损伤

Clemastine fumarate attenuates intestinal ischemia-reperfusion injury in mice

目的观察富马酸氯马斯汀(CLE)在Balb/c模型小鼠肠缺血/再灌注(I/R)损伤中的作用及其与肠组织NOD样受体蛋白3(NLRP3)炎性小体激活的关系。方法将Balb/c小鼠随机分为假手术组(sham组)、I/R组(建立肠系膜上动脉分支夹闭模型,缺血40 min,再灌注2 h)和CLE组(术前1 h,腹腔注射CLE 5 mg/kg)。肠黏膜病理改变进行Chiu’s评分;ELISA检测血清TNF-α、IL-1β及IL-18的含量;Western blot检测肠组织NLRP3、caspase-1及消皮素D(GSDMD)蛋白的表达。结果与sham组相比,I/R组Chiu’s评分明显升高(P<0.05),血清TNF-α、IL-1β及IL-18含量升高(P<0.05),肠组织NLRP3、caspase-1及GSDMD蛋白的表达量升高(P<0.05);与I/R组相比,CLE组上述指标的变化均减轻(P<0.05)。结论CLE可减轻模型小鼠肠缺血/再灌注损伤,其机制可能与调控NLRP3炎性小体的激活相关。

Objective To observe the effect of clemastine fumarate(CLE)on intestinal ischemia-reperfusion(I/R)injury in Balb/c mouse models and its correlation with the activation of intestinal NOD-like receptor protein 3(NLRP3)inflammasomes.Methods Balb/c mice were randomly divided into sham operation group,I/R group(established superior mesenteric artery branch clipping model,ischemia 40 min,reperfusion 2 h)and CLE group(intraperitoneal injection of CLE 5 mg/kg,1 h before surgery).The pathological changes of intestinal mucosa were evaluated by Chiu s score;The serum levels of TNF-α,IL-1βand IL-18 were detected by ELISA;Western blot was used to detect the expressions of NLRP3,caspase-1 and Gasdermin D proteins in intestinal tissue.Results Compared with the sham group,the Chiu s score in the I/R group significantly increased(P<0.05).The level of TNF-α,IL-1βand IL-18 in serum was increased(P<0.05).The expression of NLRP3,caspase-1 and gasdermin D(GSDMD)proteins in intestinal tissue was increased(P<0.05);Compared with the I/R group,the change of the above indexes from CLE group was alleviated(P<0.05).Conclusions CLE alleviates intestinal ischemia-reperfusion injury of mouse models and the mechanism may be related to regulation of NLRP3 inflammasome activation.