姜黄素调节NLRP3/caspase-1/GSDMD信号通路对AOPP致肺损伤大鼠细胞焦亡的影响  

Effect of curcumin on cell pyroptosis in lung injury rats caused by acute organophosphorus pesticide poisoning via regulating the NLRP3/caspase-1/GSDMD signaling pathway

作　　者：李寿彭 揭凤英 LI Shoupeng;JIE Fengying(Department of Emergency Medicine,Wuhan Third Hospital,Hubei,Wuhan 430060,China;不详)

机构地区：[1]湖北省武汉市第三医院急诊医学科,430060 [2]湖北省武汉市第三医院重症医学科,430060

出　　处：《河北医药》2025年第2期207-211,共5页Hebei Medical Journal

基　　金：湖北省自然科学基金一般面上项目(编号:2023AFB843)。

摘　　要：目的探讨姜黄素调节Nod样受体蛋白3(NLRP3)/半胱氨酸天冬氨酸蛋白酶-1(caspase-1)/消皮素D(GSDMD)信号通路对急性有机磷农药中毒(AOPP)致肺损伤大鼠细胞焦亡的影响。方法将72只SD大鼠按照随机数字表法分为control组、AOPP组、姜黄素低、中、高剂量组、阳性对照组(地塞米松),每组12只,除control组外,采用灌喂氧化乐果复制AOPP大鼠模型,各组灌胃及腹腔注射相应药物,1次/d,连续4周。HE染色观察肺组织病理损伤;TUNEL染色检测肺组织细胞焦亡;ELISA法检测血清白细胞介素-18(IL-18)、IL-1β水平;免疫组化法检测NLRP3焦亡蛋白表达;RT-qPCR检测肺组织中NLRP3、GSDMD、凋亡相关斑点样蛋白(ASC)、剪切的半胱天冬氨酸蛋白酶-1(cleaved Caspase-1)mRNA相对表达;Western blot检测肺组织中GSDMD、ASC、cleaved Caspase-1蛋白表达。结果与control组比较,AOPP组大鼠肺组织细胞焦亡率、炎性因子IL-18、IL-1β水平、ASC、NLRP3、cleaved Caspase-1、GSDMD mRNA及蛋白表达明显增高(P<0.05);与AOPP组比较,姜黄素低、中、高剂量组及阳性对照组大鼠肺组织细胞焦亡率、炎性因子IL-18、IL-1β水平、NLRP3、ASC、GSDMD、cleaved Caspase-1 mRNA及蛋白表达水平显著降低(P<0.05)。结论姜黄素可有效减轻AOPP引起的肺损伤,其作用机制可能与抑制NLRP3/caspase-1/GSDMD信号通路激活,进而抑制肺组织细胞焦亡有关。Objective To investigate the effect of curcumin on cell pyroptosis in lung injury rats caused by acute organophosphorus pesticide poisoning(AOPP)via regulating the Nod like receptor protein 3(NLRP3)/caspase-1/gasdermin D(GSDMD)signaling pathway.Methods A total of 72 Sprague Dawley(SD)rats were randomly assigned into the control group,AOPP group,low-dose,medium-dose,and high-dose curcumin groups,and positive control group(dexamethasone)using a random number table method,with 12 rats per group.Except for those in the control group,the AOPP rat model was created by gavage of omethoate,and the corresponding drugs were given by oral gavage and intraperitoneal injection once a day for 4 consecutive weeks.The hematoxylin and eosin(H&E)staining was applied to observe pathological damages in the lung tissue.The terminal deoxynucleotidyl transferase dUTP nick end-labeling(TUNEL)staining was applied to detect cell pyroptosis in the lung tissue.Enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of interleuk in-18(IL-18)and IL-1β.Immunohistochemical staining was applied to detect the protein expression of NLRP3.Reverse transcription quantitative real-time polymerase chain reaction(RT-qPCR)was applied to detect the mRNA levels of NLRP3,GSDMD,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)and cleaved caspase-1 in the lung tissue.Protein expressions of GSDMD,ASC,and cleaved Caspase-1 in the lung tissue were detected by Western blot.Results Compared with those of the control group,the cell pyroptosis rate,inflammatory factors IL-18 and IL-1βlevels,and mRNA and protein levels of ASC,NLRP3 and cleaved Caspase-1,GSDMD in rat lung tissue significantly increased in AOPP group(P<0.05).Compared with those of AOPP group,the cell pyroptosis rate,inflammatory factors IL-18 and IL-1β,and mRNA and protein levels of NLRP3,ASC,GSDMD,and cleaved Caspase-1 in rat lung tissue of low-dose,medium-dose,and high-dose curcumin groups and the positive control group were significantly reduc

关 键 词：姜黄素 NLRP3/caspase-1/GSDMD 急性有机磷农药中毒 肺损伤 细胞焦亡 

分 类 号：R563[医药卫生—呼吸系统]