基于RhoA/ROCKⅡ通路探讨原发性高血压病与炎性因子相关性研究

Exploring the correlation between primary hypertension and inflammatory factors based on RhoA/ROCKⅡ pathway

目的研究RhoA/ROCK信号通路及相关炎症因子核转录因子κBp65(NF-κBp65)、细胞间黏附分子-1(ICAM-1)、基质金属蛋白酶抑制因子1(TIMP-1)在原发性高血压病中的表达及与原发性高血压病的相关性。方法选取广安门医院于2020年8月至2020年12月收治的120例原发性高血压病患者为观察组,并纳入同期本院体检的30例无高血压病的健康人群为对照组。比较两组间静脉血Rho相关卷曲螺旋形成蛋白激酶2(ROCKⅡ)、NF-κBp65、TIMP-1、ICAM-1表达水平及静脉血单核细胞中RhoAmRNA、ROCKⅡmRNA表达水平,探究其与原发性高血压病的相关性,并以原发性高血压病的危险因素及通路相关指标ROCKⅡ、NF-κBp65、ICAM-1、TIMP-1和RhoAmRNA、ROCKⅡmRNA为自变量,是否患有原发性高血压病为因变量进行二元Logistic回归分析,绘制ROC曲线分析RhoA/ROCK通路调控的炎性因子对原发性高血压病的预测效力。结果与对照组相比,观察组ROCKⅡ、NF-κBp65、ICAM-1、TIMP-1、RhoAmRNA、ROCKⅡmRNA表达水平均有不同程度升高(P<0.05)。二元Logistic回归分析显示,ROCKⅡmRNA(OR=3.698,95%CI:1.365~10.014,P<0.05)、ROCKⅡ(OR=1.143,95%CI:1.068~1.223,P<0.001)、NF-κBp65(OR=1.486,95%CI:1.106~1.997,P<0.01)与原发性高血压病密切相关。对ROCKⅡmRNA、ROCKⅡNF-κBp65绘制与疾病相关的ROC曲线,评估参数预测效力,曲线下面积分别为ROCKⅡmRNA:0.791(95%CI:0.714~0.869,P<0.001);ROCKⅡ:0.887(95%CI:0.823~0.95,P<0.001);NF-κBp65:0.807(95%CI:0.731~0.884,P<0.001)。结论原发性高血压病病变程度与RhoAmRNA、ROCKⅡmRNA、ROCKⅡ、NF-κBp65、TIMP-1、ICAM-1变化幅度均呈正相关。并与ROCKⅡmRNA、ROCKⅡNF-κBp65密切相关。提示原发性高血压病的发生发展与RhoA/ROCKⅡ通路有密切的联系。

Objective To investigate the expression of the RhoA/ROCK signaling pathway and related inflammatory factors,nuclear transcription factorκBp65(NF-κBp65),intercellular adhesion molecule-1(ICAM-1),and matrix metalloproteinase inhibitor 1(TIMP-1)in essential hypertension and the correlation with essential hypertension disease.Methods One hundred and twenty patients with primary hypertension admitted to Guang'anmen Hospital from August 2020 to December 2020 were selected as the observation group.Furthermore,30 healthy people without hypertension who were physically examined in our hospital were included in the same period as the control group.The expression levels of venous blood Rho-related convoluted helix-forming protein kinase 2(ROCKⅡ),NF-κBp65,TIMP-1,ICAM-1,and the expression levels of RhoAmRNA and ROCKⅡmRNA in venous blood mononuclear cells were compared between the two groups to investigate their correlation with essential hypertension disease.Moreover,the pathway-related indexes ROCKⅡ,NF-κBp65,ICAM-1,TIMP-1 and RhoAmRNA,ROCKⅡmRNA as independent variables and whether or not they had primary hypertension disease dependent variables were analyzed by binary logistic regression.Moreover,ROC curves were plotted to analyze the predictive potency of RhoA/ROCK pathway-regulated inflammatory factors on primary hypertension disease.Results Compared with the control group,the expression levels of ROCKⅡ,NF-κBp65,ICAM-1,TIMP-1,RhoAmRNA,and ROCKⅡmRNA were differentially increased in the observation group(P<0.05).Spearman correlation analysis showed that primary hypertensive disease was positively correlated with the above indicators(P<0.01),and binary Logistic regression analysis showed that ROCKⅡmRNA(OR=3.698,95%CI:1.365~10.014,P<0.05),ROCKⅡ(OR=1.143,95%CI:1.068~1.223,P<0.001),NF-κBp65(OR=1.486,95%CI:1.106~1.997,P<0.01)were closely associated with primary hypertensive disease.ROC curves were plotted for ROCKⅡmRNA,ROCKⅡand NF-κBp65 in relation to disease to assess the predictive power of the parameters,and the areas under the curves were ROCKⅡmRNA:0.791(95%CI:0.714~0.869,P<0.001);ROCKⅡ:0.887(95%CI:0.823~0.95,P<0.001);NF-κBp65:0.807(95%CI:0.731~0.884,P<0.001).Conclusions The degree of primary hypertension lesions was positively correlated with the magnitude of changes in RhoAmRNA,ROCKⅡmRNA,ROCKⅡ,NF-κBp65,TIMP-1,and ICAM-1.It was also closely correlated with ROCKⅡmRNA,ROCKⅡ,and NF-κBp65.It is suggested that the development of primary hypertensive disease is closely associated with RhoA/ROCKⅡ pathway.