白藜芦醇调控ROS/NLRP3/Caspase1通路介导的细胞焦亡对重症肺炎大鼠肺损伤的保护作用

Protective effect of resveratrol on ROS/NLRP3/Caspase1 pathway⁃mediated pyroptosis on lung injury in rats with severe pneumonia

目的探讨白藜芦醇对重症肺炎大鼠肺损伤的保护作用以及活性氧簇(ROS)/NOD样受体蛋白3(NLRP3)/天冬氨酸蛋白水解酶1(Caspase1)通路在其中作用。方法取10只正常SD大鼠为空白对照组、40只SD大鼠建立重症肺炎病模型组,随机分为模型组、白藜芦醇低剂量组(6.5 mg/kg灌胃)、中剂量组(13.0 mg/kg灌胃)、高剂量组(26.0 mg/kg灌胃)各10只,空白对照组及模型组均经尾部静脉注射等体积生理盐水,连续8周。比较各组SD大鼠相关血清炎症因子水平、肺组织病理学变化、肺组织中ROS/NLRP3/Caspase1通路相关蛋白表达情况以及细胞焦亡关键蛋白Gasdermin D的N末端片段(GSDMD⁃N)的表达水平。结果干预治疗8周后,模型组TNF⁃a、IL⁃6、IL⁃1β、ROS、NLRP3、caspase⁃1和GSDMD⁃N水平>白藜芦醇低剂量组>白藜芦醇中剂量组>白藜芦醇高剂量组,差异有统计学意义(P<0.05);干预治疗8周后,与空白组SD大鼠比,模型组SD大鼠肺组织明显损伤,有大量炎症细胞浸润;模型组SD大鼠比,白藜芦醇各组SD大鼠肺泡内渗出、炎症细胞浸润等症状均明显改善。结论白藜芦醇可改善重症肺炎大鼠肺损伤,其机制可能与通过下调ROS/NLRP3/Caspase1信号通路表达水平,抑制炎症因子和细胞焦亡的发生相关。

Objective To investigate the protective effect of resveratrol on lung injury in rats with severe pneumonia and the role of reactive oxygen species(ROS)/NOD⁃like receptor protein 3(NLRP3)/aspar⁃tate proteolytic enzyme 1(Caspase1)pathway.Methods Ten normal SD rats were selected as blank control group,and 40 SD rats were used to establish severe pneumonia model group.They were randomly divided into the model group,the low⁃dose resveratrol group(6.5 mg/kg gavage),the middle⁃dose resveratrol group(13.0 mg/kg gavage)and the high⁃dose resveratrol group(26.0 mg/kg gavage),with 10 rats in each group.The blank control group and the model group were injected with equal volume of normal saline through the tail vein for 8 weeks.The levels of related serum inflammatory factors,related blood gas indexes in pulmonary artery,histopathological changes in lung tissue,the expression of ROS/NLRP3/Caspase1 pathway⁃related proteins in lung tissue and the N⁃terminal fragment of the key protein Gasdermin D(GSDMD⁃N)expression levels were compared.Results After 8 weeks of intervention,the levels of TNF⁃α,IL⁃6,IL⁃1β,ROS,NLRP3,cas⁃pase⁃1 and GSDMD⁃N in the model group>low⁃dose resveratrol group>middle⁃dose resveratrol group>high⁃dose resveratrol group(P<0.05).Compared with the blank group,the lung tissue of SD rats in the model group was significantly damaged,with many inflammatory cell infiltration;compared with SD rats in the mod⁃el group,the symptoms of alveolar exudation and inflammatory cell infiltration in SD rats in resveratrol groups were significantly improved.Conclusion Resveratrol can improve lung injury in severe pneumonia rats,and its mechanism may be related to the inhibition of inflammatory factors and pyroptosis by downregulating the ex⁃pression level of ROS/NLRP3/Caspase1 signaling pathway.