NLRP3炎症小体基因在HPV感染子宫颈细胞中的表达差异研究

Differential Expression of NLRP3 Inflammasome Gene in HPV-infected Cervical Cells

目的探讨NLRP3炎症小体相关基因在HPV感染子宫颈细胞中的差异表达及与疾病发生发展的相关性。方法收集2019年1月-2020年1月在我院进行常规HPV检测者2983例,根据检测结果分为正常组(1222例,常规HPV检测阴性)、低危HPV组(1023例)、高危HPV组(738例),比较各组一般临床资料,对低危HPV组和高危HPV组患者进行阴道镜检查并进行阴道镜下子宫颈组织活检;随访2年后对低危HPV组和高危HPV组再次进行检查,每组根据有无出现子宫颈上皮内瘤变(CIN)分为CIN亚组和non-CIN亚组。利用反转录-聚合酶链反应(RT-PCR)技术检测NLRP3炎症小体相关基因NLRP3、Caspase-1、IL-18、IL-1β、NF-kB和ASC的mRNA表达,蛋白质免疫印迹法(Western blot)检测其蛋白表达。结果与正常组比较,低危HPV组和高危HPV组NLRP3、Caspase-1、IL-18、IL-1β、NF-kB的mRNA和蛋白表达水平均升高,差异有统计学意义(P<0.05),但3组ASC的mRNA表达比较,差异有统计学意义(P<0.05),而蛋白表达水平比较,差异无统计学意义(P>0.05);随访2年后,低危HPV组有409例发生CIN,高危HPV组有421例发生CIN,各组CIN组的NLRP3、Caspase-1、IL-18、IL-1β、NF-kB和ASC的mRNA和蛋白表达水平均高于non-CIN组,差异有统计学意义(P<0.05)。结论NLRP3炎症小体可能是HPV感染宫颈病变过程中重要的分子事件,NLRP3炎症小体有可能作为HPV感染宫颈病变的预测标志物。

Objective To investigate the differential expression of NLRP3 inflammasome-related genes in HPV-infected cervical cells and its correlation with the occurrence and development of the disease.Methods A total of 2983 patients who underwent routine HPV test in our hospital from January 2019 to January 2020 were collected.According to the test results,they were divided into normal group(1222 cases,negative for routine HPV test),low-risk HPV group(1023 cases)and high-risk HPV group(738 cases).The general clinical data of each group were compared.The patients in the low-risk HPV group and the high-risk HPV group were examined by colposcopy and cervical biopsy under colposcopy.After 2 years of follow-up,the low-risk HPV group and the high-risk HPV group were examined again.Each group was divided into CIN subgroup and non-CIN subgroup according to the presence or absence of cervical intraepithelial neoplasia(CIN).The mRNA expression of NLRP3 inflammasome-related genes NLRP3,caspase-1,IL-18,IL-1β,NF-kB and ASC was detected by reverse transcription-polymerase chain reaction(RT-PCR),and the protein expression was detected by Western blot.Results Compared with the normal group,the mRNA and protein expression levels of NLRP3,caspase-1,IL-18,IL-1βand NF-kB in the low-risk HPV group and the high-risk HPV group were increased,and the difference was statistically significant(P<0.05).However,there was a statistically significant difference in the mRNA expression of ASC among the three groups(P<0.05),but there was no significant difference in the protein expression level(P>0.05).After 2 years of follow-up,there were 409 cases of CIN in the low-risk HPV group and 421 cases of CIN in the high-risk HPV group.The mRNA and protein expression levels of NLRP3,caspase-1,IL-18,IL-1β,NF-kB and ASC in CIN subgroups were higher than those in non-CIN subgroups,and the differences were statistically significant(P<0.05).Conclusion NLRP3 inflammasome may be an important molecular event in the process of HPV infected cervical lesions,and NLRP3 inflammasome may be used as a predictive marker for HPV infected cervical lesions.