Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway  

作　　者：GUO Fan HAN Xiao YOU Yue XU Shu-juan ZHANG Ye-hao CHEN Yuan-yuan XIN Gao-jie LIU Zi-xin REN Jun-guo CAO Ce LI Ling-mei FU Jian-hua 

机构地区：[1]Institute of Basic Medical Sciences of Xiyuan Hospital,ChinaAcademy of Chinese Medical Sciences,Beijing 100091,China [2]Beijing Key Laboratory of Chinese Materia Pharmacology,Beijing 100091,China [3]Department of Central Laboratory,Kunshan Hospital of Chinese Medicine,Kunshan,JiangsuProvince 215300,China

出　　处：《Chinese Journal of Integrative Medicine》2024年第11期1027-1034,共8页中国结合医学杂志（英文版）

基　　金：Supported by the Youth Planning Project of Beijing Scienceand Technology Development Fund for Chinese Medicine(No.QN-2020-14);innovation Fund of China Academy of ChineseMedical Sciences(No.CI2021A00912);Scientific Fund ofNational Clinical Research Center for Chinese Medicine Cardiology(No.CMC2022005)。

摘　　要：Objective:To observe the protective effect and mechanism of hydroxyl safflower yellow A(HsYA)from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells(HUVECs).Methods:HUVECs were treated with oxygen-glucose deprivation reperfusion(OGD/R)to simulate the ischemia reperfusion model,and cell counting kit-8 was used to detect the protective effect of different concentrations(1.25-160μmol/L)of HSYA on HUVECs after OGD/R.HSYA 80μmol/L was used for follow-up experiments.The contents of inflammatory cytokines interleukin(IL)-18,IL-1β,monocyte chemotactic protein 1(MCP-1),tumor necrosis factorα(TNF-α)and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay.The protein expressions of toll-like receptor,NOD-like receptor containing pyrin domain 3(NLRP3),gasdermin D(GSDMD)and GSDMD-N-terminal domain(GSDMD-N)before and after administration were detected by Western blot.NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt(CRID3 sodium salt,also known as MCC950)and agonist were added,and the changes of NLRP3,cysteine-aspartic acid protease 1(Caspase-1),GSDMD and GSDMD-N protein expressions were detected by Western blot.Results:HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18,IL-1β,MCP-1,TNF-αandIL-6(P<0.01or P<0.05).At the same time,by inhibiting NLRP3/Caspase-1/GSDMD pathway,HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3,Caspase-1,GSDMD and GSDMD-N proteins(P<0.01).Conclusions:The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

关 键 词：NLRP3 inflammasome hydroxysafflor yellow A Chinese medicine human umbilical vein endothelial cells PYROPTOSIS myocardial reperfusion injury oxygen-glucose deprivation reperfusion 

分 类 号：R285[医药卫生—中药学]