NLRP3炎症小体的表达及多态性与急性冠脉综合征患者Caspase-1水平和冠脉病变程度的关系研究

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摘要目的研究急性冠脉综合征（ACS）患者体内Nod 样受体蛋白3（NLRP3）炎性小体的表达及多态性与Caspase-1 水平、冠脉病变程度的关系。方法选取2018年1月～2019年5月在沈阳医学院附属第二医院心内科住院的150 例临床诊断为ACS 的患者作为实验组，选取同期的疑似冠心病入院但行选择性冠状动脉造影术检查阴性的50 例患者作为对照组。采集外周血并检测NLRP3 基因rs10754558 位点的多态性，分离血清并测定炎性小体活性指标，同时进行冠状动脉造影。比较两组患者的NLPR3、Caspase-1 表达水平，根据冠状动脉造影检查结果，记录不同冠脉病变支数的NLPR3、Caspase-1 表达水平及Gensini 评分；观察不同NLRP3 基因型患者的冠脉病变情况，分析NLRP3 表达及多态性与急性冠脉综合征患者Caspase-1水平和冠脉病变程度的关系。结果实验组的NLPR3 和Caspase-1 表达水平高于对照组（P＜0.05）。实验组三支病变患者的NLPR3、Caspase-1 表达水平及Gensini评分高于双支病变及单支病变患者，双支病变患者的NLPR3、Caspase-1 表达水平及Gensini 评分高于单支病变患者，差异有统计学意义（P＜0.05）。Pearson 相关性分析显示，NLPR3 表达水平与Caspase-1 表达水平、Gensini 评分成正相关（r=0.714、0.781，P＜0.05）。实验组中NLRP3 基因rs10754558 位点基因型中，CC 基因型44 例（29.33%），GG 基因型46 例（30.67%），GC 基因型60 例（40.00%）；对照组NLRP3 基因rs10754558 位点基因型中，CC 基因型40 例（80.00%），GG 基因型4 例（8.00%），GC 基因型6 例（12.00%）。实验组NLRP3 基因中的GG 基因型和GC 基因型所占比例高于对照组，CC 基因型所占比例低于对照组，差异有统计学意义（P＜0.05）。实验组中，三支病变多见于NLPR3 的GG 型和GC 型。结论 ACS 患者体内的NLPR3 表达水平与Caspase-1 表达水平、Gensini 评分成正相关，NLRP3 基因rs10754558 位点等位基因G 增多会增加炎性小体活性，预示患者冠脉病变重，预后不良。

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	吴蔚
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	张晶
	田鑫

关键词 ：急性冠脉综合征, NLPR3, 炎性小体, 基因多态性

Abstract：Objective To study the relationship between the expression and polymorphism of inflammatory bodies of Nod like receptor protein 3 (NLRP3) and the level of Caspase-1 and the degree of coronary lesions in patients with acute coronary syndrome (ACS).Methods From January 2018 to may 2019,150 patients with ACS diagnosed clinically in the Department of Cardiology of the Second Affiliated Hospital of Shenyang Medical College were selected as the experimental group,50 patients suspected with coronary heart disease admitted to hospital during the same period but who underwent negative coronary angiography examination were selected as the control group.The peripheral blood was collected and the rs10754558 polymorphism of NLRP3 gene was detected.The serum was isolated and the activity index of inflammatory body was measured.Coronary angiography was performed at the same time.The expression levels of NLPR3 and Caspase-1 were compared between the two groups.According to the results of coronary angiography,the expression levels of NLPR3 and Caspase-1 and the Gensini scores of different coronary lesions were recorded.The coronary lesions of different NLRP3 genotypes were observed,and the relationship between the expression and polymorphism of NLRP3 and the level of Caspase-1 and the degree of coronary lesions were analyzed.Results The expression levels of NLPR3 and Caspase-1 in the experimental group were higher than those in the control group (P＜0.05).In the experimental group,the expression levels of NLPR3,Caspase-1 and Gensini score in the patients with three vessel lesions were higher than those in the patients with two vessel lesions and single vessel lesion,the expression levels of NLPR3,Caspase-1 and Gensini score in patients with two vessel lesions were higher than those in patients with single vessel lesion,the differences were statistically significant (P＜0.05).Pearson correlation analysis showed that NLPR3 expression level was positively correlated with Caspase-1 expression level and Gensini score (r=0.714,0.781,P＜0.05).Among the rs10754558 genotypes of NLRP3 gene in the experimental group,44 cases (29.33%)were CC genotype,46 cases (30.67%)were GG genotype,and 60 cases(40.00%) were GC genotype.In the rs10754558 genotypes of NLRP3 gene in the control group,40 cases (80.00%) were CC genotype,4 cases (8.00%) were GG genotype and 6 cases (12.00%) were GC genotype.The proportions of GG genotype and GC genotype in NLRP3 gene of the experimental group were higher than those of control group,and the proportion of CC genotype in NLRP3 gene of the experimental group was lower than that of control group,the differences were statistically significant (P＜0.05).In the experimental group,the three branches lesions were mostly seen in the GG and GC types of NLPR3.Conclusion The expression of NLPR3 in ACS patients is positively correlated with Caspase-1 expression level and Gensini score.The increase of allele g at rs10754558 of NLRP3 gene can increase the activity of inflammatory bodies,indicating the severity of coronary lesions and poor prognosis.

Key words： Acute coronary syndrome NLPR3 Inflammatory corpuscle Gene polymorphism

基金资助:辽宁省沈阳市科技计划项目（18-014-4-52）

作者简介: 吴蔚（1970-），硕士，主任医师，硕士生导师，主要从事冠心病的基础与临床研究

引用本文:

吴蔚；王晓萍；孙琳；倪青；邵冰；张晶；田鑫. NLRP3炎症小体的表达及多态性与急性冠脉综合征患者Caspase-1水平和冠脉病变程度的关系研究[J]. 中国当代医药, 2021, 28(1): 71-74.
WU Wei ；WANG Xiao-ping； SUN Lin； NI Qing； SHAO Bing ；ZHANG Jing； TIAN Xin. Relationship study between the expression and polymorphism of NLRP3 inflammatory bodies and the level of Caspase-1 and the degree of coronary lesions in patients with acute coronary syndrome. 中国当代医药, 2021, 28(1): 71-74.

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http://dangdaiyiyao.com/CN/ 或 http://dangdaiyiyao.com/CN/Y2021/V28/I1/71

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