动脉瘤性蛛网膜下腔出血患者血清Cav-1、FoxO3a mRNA表达水平及与预后的关系

Expression of serum Cav-1 and FoxO3a mRNA in patients with aneurysmal subarachnoid hemorrhage and its relationship with prognosis

目的 分析动脉瘤性蛛网膜下腔出血(aSAH)患者血清小窝蛋白-1(Cav-1)、叉头框蛋白O3a(FoxO3a)信使RNA(mRNA)表达水平及与预后的关系。方法 选取2018年11月—2021年12月首都医科大学附属北京友谊医院平谷医院收治的aSAH患者128例为aSAH组,另选取同期医院健康体检者95例为健康对照组。对aSAH患者出院后随访6个月,根据格拉斯哥预后评分(GOS)分为预后良好亚组87例(GOS评分>3分)和预后不良亚组41例(GOS评分≤3分)。比较aSAH组与健康对照组、不同预后患者血清Cav-1、FoxO3a mRNA表达水平,以及不同预后患者临床资料;多因素Logistic回归分析影响aSAH患者预后的危险因素;受试者工作特征曲线(ROC)分析血清Cav-1、FoxO3a mRNA对aSAH患者预后的评估价值。结果 与健康对照组比较,aSAH组患者血清Cav-1表达水平显著降低,FoxO3a mRNA表达水平显著升高(t/P=12.955/<0.001、34.392/<0.001);预后不良亚组患者血清Cav-1水平显著低于预后良好亚组,FoxO3a mRNA表达水平高于预后良好亚组(t/P=12.853/<0.001、20.488/<0.001);预后不良亚组患者高血压史、糖尿病史、改良Fisher分级Ⅲ~Ⅳ级、Hung-Hess分级Ⅲ~Ⅳ级、WFNS分级Ⅳ~Ⅴ级、动脉瘤直径>10 mm比例显著高于预后良好亚组(χ^(2)/P=4.748/0.029、4.579/0.032、18.361/<0.001、7.634/0.006、8.388/0.004、7.255/0.007);Logistic回归分析结果显示,改良Fisher分级高、Hung-Hess分级高、血清FoxO3a mRNA水平高是aSAH患者预后不良的危险因素[OR(95%CI)=3.721(1.913~7.253)、3.864(1.730~8.631)、8.291(2.888~23.799)],血清Cav-1水平高是其保护因素[OR(95%CI)=0.496(0.340~0.723)];血清Cav-1、FoxO3a mRNA及二者联合评估aSAH患者预后的ROC曲线下面积分别为0.855、0.832、0.902,二者联合评估效能高于单项预测(Z/P=2.121/0.034、2.623/0.009)。结论 aSAH患者血清Cav-1呈低表达、FoxO3a mRNA呈高表达,是影响aSAH患者预后的因素,二者联合检测对aSAH患者的预后有一定的评估价值。

Objective To analyze the expression levels of serum caveolin-1(Cav-1) and forkhead box protein O3a(FoxO3a) messenger RNA(mRNA) in patients with aneurysmal subarachnoid hemorrhage(aSAH) and their relationship with prognosis. Methods One hundred and twenty eight patients with aSAH admitted to Pinggu Hospital of Beijing Friendship Hospital Affiliated to Capital Medical University from November 2018 to December 2021 were selected as the aSAH group, and 95 patients with physical examination in the same period were selected as the health control group. The patients with aSAH were followed up for 6 months after discharge. According to Glasgow Outcome Scale(GOS), they were divided into 87 patients with good prognosis(GOS score>3 points) and 41 patients with poor prognosis(GOS score ≤ 3 points). The expression levels of serum Cav-1, FoxO3a mRNA and clinical data of patients with different prognosis were compared between the aSAH group and the healthy control group;Multivariate logistic regression analysis was used to analyze the risk factors affecting the prognosis of patients with aSAH;The prognostic value of serum Cav-1 and FoxO3a mRNA in patients with aSAH was analyzed by receiver operating characteristic curve(ROC). Results Compared with the healthy control group, the serum Cav-1 expression level of patients in the aSAH group decreased significantly, and the FoxO3a mRNA expression level increased significantly(t/P=12.955/<0.001, 34.392/<0.001). The serum Cav-1 level in patients with poor prognosis was significantly lower than that in patients with good prognosis, and the expression level of FoxO3a mRNA was higher than that in patients with good prognosis(t/P=12.853/<0.001, 20.488/<0.001). The proportion of hypertension history, diabetes history, modified Fisher grade Ⅲ-Ⅳ, Hung Hess grade Ⅲ-Ⅳ, WFNS grade Ⅳ-Ⅴ, aneurysm diameter>10 mm in poor prognosis subgroup was significantly higher than that in good prognosis subgroup(χ^(2)/P=4.748/0.029, 4.579/0.032, 18.361/<0.001、7.634/0.006, 8.388/0.004, 7.255/0.007). Logistic regression analysis showed that high modified Fisher grade, high Hung Hess grade and high level of serum FoxO3a mRNA were risk factors for poor prognosis of patients with aSAH [OR(95%CI)=3.721(1.913-7.253), 3.864(1.730-8.631), 8.291(2.888-23.799)].High level of serum Cav-1 was a protective factor [OR(95% CI)=0.496(0.340-0.723)].The area under the ROC curve of serum Cav-1, FoxO3a mRNA and their combination to evaluate the prognosis of patients with aSAH were 0.855, 0.832 and 0.902 respectively, and their combined evaluation efficiency was higher than that of single prediction(Z/P=2.121/0.034, 2.623/0.009). Conclusion The low expression of serum Cav-1 and high expression of FoxO3a mRNA in patients with aSAH are factors that affect the prognosis of patients with aSAH. The combined detection of the two has certain evaluation value for the prognosis of patients with aSAH.