NLRP1及NLRP3在溃疡性结肠炎患者结肠组织中的表达及其临床意义

Expression and clinical significance of NLRP1 and NLRP3 in colonic tissues of patients with ulcerative colitis

目的探讨溃疡性结肠炎(ulcerative colitis,UC)患者结肠黏膜组织中NLRP1及NLRP3的表达,并分析其与UC病情严重程度、内镜下病变严重程度及实验室指标的相关性。方法收集46例UC患者(轻度22例,中重度24例)和20例正常对照者的结肠镜活检标本,采用免疫组化法及荧光定量PCR法检测结肠黏膜组织中NLRP1和NLRP3的蛋白和mRNA表达,并分析两者的蛋白表达与UC患者的Mayo总体评分、Mayo内镜评分、血沉、C-反应蛋白、血尿酸、低密度脂蛋白、胆固醇、血小板水平的相关性。结果UC患者结肠黏膜组织中NLRP1与NLRP3蛋白及mRNA的表达明显高于正常对照组(P<0.05);与轻度UC相比,中重度UC患者的结肠黏膜组织中NLRP1表达明显升高(P<0.05)。不同病变范围UC患者结肠黏膜组织中NLRP1及NLRP3表达无明显差异;NLRP1表达与Mayo总体评分、Mayo内镜评分及血沉、C-反应蛋白均呈正相关(P<0.05),NLRP3表达与C反应蛋白呈正相关(P<0.05),与Mayo总体评分、Mayo内镜评分、血沉无相关性;NLRP1表达与低密度脂蛋白、血小板呈正相关(P<0.05),但与血尿酸、胆固醇无相关性。NLRP3与低密度脂蛋白、血尿酸、胆固醇呈正相关(P<0.05),但与血小板无相关性。结论NLRP1及NLRP3可能参与了UC的发病过程且与疾病的活动性有关,可作为靶向治疗的分子靶标,NLRP1可能作为黏膜愈合的预测指标。

Objective To investigate the expressions of NLRP1 and NLRP3 in the colon of ulcerative colitis(UC)patients and analyze the correlation of the expressions with severity of UC,endoscopic manifestations and related laboratory indicators.Methods We collected biopsical specimens obtained with colonoscopy in 46 patients with UC(22 mild cases and 24 moderate to severe cases)and 20 cases of normal control group.We used the disease activity index to evaluate the Mayo UC inflammatory activity and immunohistochemical method to detect the protein expression levels of intestinal mucosal NLRP1 and NLRP3 in the tissue.RT-PCR was used to detect the expressions of NLRP1 and NLRP3 mRNA in intestinal mucosal tissues.Meanwhile,the colonoscopy,serum uric acid,C-reactive protein,serum sedimentation rate,platelet count,low-density lipoprotein,and cholesterol of UC patients were also counted to further analyze the relationship between NLRP1 and NLRP3.Results The expressions ofNLRP1 and NLRP3 protein and mRNA in colonic mucosal tissues of UC patients were significantly higher than those of normal controls(P<0.05).Compared with that in mild UC,the expression of NLRP1 in colonic mucosal tissues of moderate and severe UC patients was significantly increased(P<0.05).There was no significant difference in the expressions of NLRP1 and NLRP3 in colonic mucosal tissues of UC patients with different lesion ranges.NLRP1 expression was positively correlated with Mayo overall score,Mayo endoscopic score,erythrocyte sedimentation rate,and C-reactive protein(P<0.05),NLRP3 expression was positively correlated with C-reactive protein(P<0.05),but not correlated with Mayo overall score,Mayo endoscopic score,or erythrocyte sedimentation rate.NLRP1 expression was positively correlated with low-density lipoprotein and platelet(P<0.05),but not with uric acid or cholesterol.NLRP3 was positively correlated with low-density lipoprotein,uric acid and cholesterol(P<0.05),but not with platelet.Conclusion NLRP1 and NLRP3 may be involved in the pathogenesis of UC and related to disease activity.Therefore,they can be used as molecular targets for targeted therapy,and NLRP1 can be used as a predictor of mucosal healing.