益母草水苏碱调控HIF-1α泛素化抑制焦亡减轻肺缺血再灌注损伤实验研究

Experimental Study on Stachydrine Attenuates Lung Ischemia-Reperfusion Injuryby Regulating HIF-1αUbiquitination to Inhibit Pyroptosis

目的:观察益母草水苏碱(STA)对肺缺血再灌注损伤的影响,并探讨其可能机制。方法:将30只SD大鼠随机分为Control组、IR组和STA+IR组,每组10只。取肺组织病理切片HE染色,使用免疫荧光和蛋白质印迹法检测各组大鼠肺组织HIF-1α、SUMO-HIF-1α、NLRP3、GSDMD蛋白的表达水平;应用RT-qPCR检测各组大鼠肺组织IL-6和IL-1βmRNA的表达水平。结果:结果显示,与Control组相比,IR组大鼠肺组织病理切片可见大量单核粒细胞浸润,SUMO-HIF-1α明显降低,NLRP3及GSDMD表达均升高,炎症因子IL-6、IL-1β水平升高(P<0.05);与IR组相比,STA处理IR后可见肺组织损伤和炎症明显减少,SUMO-HIF-1α明显升高,NLRP3及GSDMD表达均明显降低,炎症因子IL-6、IL-1β水平降低(P<0.05)。结论:STA对缺血再灌注损伤大鼠肺损伤具有保护作用,其机制可能是通过调控HIF-1α泛素化从而抑制NLRP3焦亡通路。

Objective:To observe the effect of stachydrine(STA)on pulmonary ischemia-reperfusion injury and to explore its possible mechanism.Methods:Thirty SD rats were randomLy divided into Control group,IR group and STA+IR group,10 rats in each group.The expression levels of HIF-1α,SUMO-HIF-1α,NLRP3 and GSDMD proteins in lung tissues of rats in each group were detected by immunofluorescence and protein blotting;the expression levels of IL-6 and IL-1βmRNA in lungtissues of rats in each group were detected by RT-qPCR.Results:The results showed that compared with the Control group,In the histopathological sections of the lungs of rats in the IR group,a large number of mononuclear granulocytic infiltrations were observed,SUMO-HIF-1αreduced significantly,and increased expression of NLRP3 and GSDMD,and increased levels of inflammatory factors IL-6 and IL-1β(P<0.05);Compared with the IR group,STA treatment of IR Compared with the IR group,lung tissue injury and inflammation were significantly reduced,SUMO-HIF-1αwas significantly increased,NLRP3 and GSDMD expression were significantly reduced,and the levels of inflammatory factors IL-6 and IL-1βwere reduced after STA treatment(P<0.05).Conclusion:STA has a protective effect on lung injury in rats with ischemia-reperfusion injury,and the mechanism may be through the regulation of HIF-1αubiquitination to inhibit NLRP3 pyroptosis pathway.