NLRP3炎性小体及其上游激活蛋白GSDMD在原发性胆汁性肝硬化中的表达  

Expression of NLRP3 inflammasome body and its upstream activator GSDMD in primary biliary cirrhosis

作　　者：向国艳 樊佳 叶震璇[3] 付雪 张海燕[3] 张华[3,4] XIANG Guoyan;FAN Jia;YE Zhenxuan;FU Xue;ZHANG Haiyan;ZHANG Hua(Teaching and Researching Section of Clinical Laboratory,Guizhou Medical University,Guiyang,Guizhou 550004,China;Department of Clinical Laboratory,Traditional ChineseMedicine Hospital Affiliated to Southwest Medical University,Luzhou,Sichuan 646000,China;Department of Clinical Laboratory,Guizhou Provincial People′s Hospital,Guiyang,Guizhou 550002,China;School of Clinical Laboratory Science,GuizhouMedical University,Guiyang,Guizhou 550004,China)

机构地区：[1]贵州医科大学临检教研室,贵州贵阳550004 [2]西南医科大学附属中医医院检验科,四川泸州646000 [3]贵州省人民医院检验科,贵州贵阳550002 [4]贵州医科大学医学检验学院,贵州贵阳550004

出　　处：《国际检验医学杂志》2019年第17期2049-2052,2057,共5页International Journal of Laboratory Medicine

基　　金：贵州省人民医院国家自然科学基金培育基金项目(黔科合LH字[2017]5724号)

摘　　要：目的 初步探讨核苷酸结合寡聚化结构域样受体3(NLRP3)及其上游激活蛋白gasderminD(GSDMD)与原发性胆汁性肝硬化(PBC)免疫炎性反应的关联。方法 收集就诊于贵州省人民医院的患者外周血血浆,采用生化分析仪检测肝功能,间接免疫荧光法检测抗线粒体抗体(AMA),免疫印记法检测抗线粒体M2型抗体(AMA-M2)。以肝功能出现异常且AMA或AMA-M2阳性来确诊PBC患者。分别收集30例PBC患者(PBC组)与30例体检健康者(健康对照组),采用q-PCR与Westernblot分别检测两组外周血单个核细胞中NLRP3与GSDMD的mRNA和蛋白的表达量。采用ELISA检测Caspase-1和白细胞介素(IL)-18在血浆中的表达量。结果 PBC患者肝功能各项指标测量值均高于健康对照组(P<0.05),且AMA或AMA-M2为阳性。PBC患者外周血单个核细胞中NLRP3、GSDMD的mRNA和蛋白表达均高于健康对照组(P<0.05)。Caspase-1、IL-18在PBC组血浆中的表达水平高于健康对照组(P<0.05)。结论 NLRP3与GSDMD可能参与了PBC的免疫炎性反应。Objective To investigate the relationship between nucleotide binding oligomerization domain-like receptor 3 (NLRP3) and its upstream activator gasdermin D (GSDMD) and immunoinflammasome response in primary biliary cirrhosis (PBC). Methods Peripheral blood plasma was collected from patients in Guizhou Provincial People′s Hospital.Liver function was detected by biochemical analyzer.Indirect immunofluorescence assay was used to detect anti-mitochondrial antibody (AMA) and immunoblotting to detect anti-mitochondrial M2 antibody (AMA-M2).Patients with PBC were diagnosed with abnormal liver function and positive AMA or AMA-M2.The expressions of NLRP3 and GSDMD in peripheral blood mononuclear cells (PBMC) of 30 PBC patients (PBC group) and 30 healthy persons (healthy control group) were detected by q-PCR and Western blot.The expressions of Caspase-1 and interleukin-18 (IL-18) in plasma were detected by ELISA. Results The measured values of liver function test items in patients with PBC were higher than those in healthy controls ( P <0.05),and AMA or AMA-M2 were positive.The mRNA and protein expression of NLRP3 and GSDMD in PBC patients was higher than that in healthy control group ( P <0.05),and the expression of Caspase-1 and IL-18 in PBC patients was higher than that in healthy control group ( P <0.05). Conclusion NLRP3 and GSDMD may be involved in the immune inflammasome response of PBC.

关 键 词：核苷酸结合寡聚化结构域样受体3 gasderminD 原发性胆汁性肝硬化 

分 类 号：R657.3[医药卫生—外科学] R446.1[医药卫生—临床医学]