急性脑梗死患者血清miR-22-3p、NLRP3水平与炎性因子及预后不良的关系

The relationship between serum miR-22-3p and NLRP3 levels,inflammatory factors,and poor prognosis in patients with acute cerebral infarction

目的探讨急性脑梗死(ACI)患者血清微小核糖核酸-22-3p(miR-22-3p)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)水平与炎性因子及预后不良的关系。方法选取2021年1月—2022年12月上海中医药大学附属第七人民医院神经内科收治ACI患者106例为ACI组,根据预后情况分为预后不良亚组37例和预后良好亚组69例,另选取同期体检健康者60例为健康对照组。采用实时荧光定量聚合酶链式反应检测血清miR-22-3p水平,酶联免疫吸附法检测血清NLRP3和炎性因子[白介素(IL)-1β、IL-18、肿瘤坏死因子-α(TNF-α)]水平。通过Pearson相关性分析ACI患者血清miR-22-3p、NLRP3与IL-1β、IL-18、TNF-α的相关性。分析ACI患者预后不良的影响因素,绘制2项指标的受试者工作特征(ROC)曲线分析其预测预后的价值。结果与健康对照组比较,ACI组血清miR-22-3p水平降低,NLRP3、IL-1β、IL-18、TNF-α水平显著升高(t/P=18.698/<0.001、27.091/<0.001、30.154/<0.001、35.104/<0.001、39.834/<0.001)。Pearson相关性分析显示,ACI患者血清miR-22-3p与NLRP3、IL-1β、IL-18、TNF-α水平呈负相关(r/P=-0.733/<0.001、-0.719/<0.001、-0.683/<0.001、-0.680/<0.001),血清NLRP3与IL-1β、IL-18、TNF-α水平呈正相关(r/P=0.716/<0.001、0.715/<0.001、0.707/<0.001)。多因素Logistic回归分析显示,NIHSS评分、IL-1β、IL-18、TNF-α、NLRP3升高为ACI患者预后不良的独立危险因素[OR(95%CI)=1.244(1.034~1.497)、1.373(1.067~1.767)、1.047(1.011~1.086)、1.577(1.061~2.343)、1.084(1.022~1.149)],miR-22-3p升高为独立保护因素[OR(95%CI)=0.933(0.888~0.980)]。ROC曲线分析显示,血清miR-22-3p、NLRP3水平联合预测ACI患者预后不良的曲线下面积为0.875,大于两者单独预测的0.786、0.759(Z/P=2.405/0.016、2.517/0.012)。结论ACI患者血清miR-22-3p水平降低和NLRP3水平升高,与炎性因子水平升高和预后不良密切相关,血清miR-22-3p、NLRP3水平联合对ACI患者预后不良的预测价值较高。

Objective To investigate the relationship between serum levels of microribonucleic acid 22-3p(miR-22-3p)and NOD like receptor heat protein domain related protein 3(NLRP3)in patients with acute cerebral infarction(ACI),inflammatory factors,and poor prognosis.Methods One hundred and six patients with ACI admitted to the Neurology Department of the Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2021 to December 2022 were selected as the ACI group.According to the prognosis,they were divided into a subgroup of 37 patients with poor prognosis and a subgroup of 69 patients with good prognosis.Additionally,60 healthy individuals who underwent physical examinations during the same period were selected as the healthy control group.Real time fluorescence quantitative polymerase chain reaction was used to detect serum miR-22-3p levels.Enzyme-linked immunosorbent assay for detecting serum NLRP3 and inflammatory factors[interleukin(IL-1)]β,IL-18,Tumor Necrosis Factor-α(TNF-α)].Pearson was used to analyze the relationship between serum miR-22-3p and NLRP3 with IL-1β,IL-18 and TNF-αin ACI patients.Analyze the influencing factors of poor prognosis in ACI patients and draw subject operating characteristic(ROC)curves for two indicators.Results Compared with the healthy control group,the serum levels of miR-22-3p in the ACI group decreased,and the levels of NLRP3,IL-1β,IL-18 and TNF-αincreased(t/P=18.698/<0.001,27.091/<0.001,30.154/<0.001,35.104/<0.001,39.834/<0.001).Pearson correlation analysis showed that serum miR-22-3p was negatively correlated with the levels of NLRP3,IL-1β,IL-18 and TNF-αin ACI patients(r/P=-0.733/<0.001,-0.719/<0.001,-0.683/<0.001,-0.680/<0.001),and serum NLRP3 was positively correlated with the levels of IL-1β,IL-18 and TNF-α(r/P=0.716/<0.001、0.715/<0.001、0.707/<0.001).Multivariate Logistic regression analysis showed that elevated NIHSS score,IL-1β,IL-18,TNF-α,and NLRP3 were independent risk factors for poor prognosis in patients with ACI[OR(95%CI)=1.244(1.034-1.497),1.373(1.067-1.767),1.047(1.011-1.086),1.577(1.061-2.343),1.084(1.022-1.149)],miR-22-3p was the independent protection factor[OR(95%CI)=0.933(0.888-0.980)].ROC curve analysis showed that the area under the curve of serum miR-22-3p and NLRP3 levels combined to predict the poor prognosis of ACI patients was 0.875,which was greater than that predicted by the two alone(0.786 and 0.759(Z/P=2.405/0.016 and 2.517/0.012).Conclusion The decrease of serum miR-22-3p level and the increase of NLRP3 level in ACI patients are closely related to the increase of inflammatory factor levels and poor prognosis,and the combined serum levels of miR-22-3p and NLRP3 have a high predictive value for poor prognosis in ACI patients.