罗伊氏黏液乳杆菌通过抑制ROS依赖性NLRP3炎性通路缓解大鼠肠缺血/再灌注损伤

Limosilactobacillus reuteri Alleviates Intestinal Ischemia/Reperfusion Injury in Rats by Inhibiting the ROS Dependent NLRP3 Inflammatory Pathway

本研究旨在以ROS/NLRP3炎性小体为切入点,探讨罗伊氏黏液乳杆菌(Limosilactobacillus reuteri,LR)改善肠缺血性再灌注损伤(intestinal ischemia-reperfusion injury,IR)的作用机制。通过缺氧/复氧方法来构建IR细胞模型,以及微动脉夹夹闭/灌注方法来构建大鼠IR模型。细胞试验分为4组,对照组、缺血再灌注细胞模型组、罗伊氏黏液乳杆菌预处理组、罗伊氏黏液乳杆菌组。动物试验分为3组(每组10只大鼠),假手术组、缺血再灌注损伤组、罗伊氏黏液乳杆菌灌胃处理组。检测各组ROS水平,NLRP3炎性小体相关蛋白(NLRP3、ASC、Caspase p10、GSDMD)表达情况,炎性相关指标(TNF-α、IL-1β、IL-6、IL-10)水平,氧化应激相关指标(ROS、SOD、GSH-Px、MDA)含量,并进行病理组织学评价。结果显示,1)罗伊氏黏液乳杆菌可以减弱IR导致的氧化应激以及NLRP3炎性小体的激活。2)罗伊氏黏液乳杆菌通过减弱ROS的表达来缓解NLRP3炎性小体的激活。3)罗伊氏黏液乳杆菌能够缓解IR对肠道组织的损伤,以及炎性因子的表达。综上所述,LR可缓解大鼠肠IR和氧化应激,其作用机制与抑制ROS依赖性NLRP3炎性小体有关,为LR在肠道相关疾病的兽医临床治疗提供试验依据。

The aim of this study is to explore the mechanism of Limosilactobacillus reuteri(LR)improving intestinal ischemia-reperfusion injury(IR)using ROS/NLRP3 inflammasome as a starting point.The IR cell model was constructed using hypoxia/reoxygenation methods,and the rat IR model was constructed using microarterial clamping/perfusion methods.The cell experiment was divided into four groups:control group,IR group,LR pre-treatment group(LR+IR group),and LR group.The animal experiment was divided into three groups(10 rats in each group):sham surgery group(S group),IR group,and LR gavage treatment group(LR+IR group).The level of ROS,the expression of NLRP3 inflammasome related proteins(NLRP3,ASC,Caspase p10,and GSDMD),the levels of inflammation-related indicators,and the content of oxidative stress related indicators in each group were detected.Histopathological evaluation was also performed.The results showed that:1)LR attenuates IR induced oxidative stress and NLRP3 inflammasome activation.2)LR alleviates NLRP3 inflammasome activation by attenuating ROS expression.3)LR could alleviate intestinal injury and the expression of inflammatory factors induced by IR.In summary,LR can alleviate intestinal IR and oxidative stress in rats,and its mechanism of action is related to the inhibition of ROS dependent NLRP3 inflammasome,providing experimental basis for the veterinary clinical treatment of LR in intestinal related diseases.