SIRT1/NF-κB信号通路与脑梗死后认知障碍风险及认知障碍程度的相关性分析

Correlation analysis of the SIRT1/NF-κB signaling pathway with the risk and severity of cognitive impairment following cerebral infarction

摘要:

目的 探讨沉默信息调节因子2相关酶1（SIRT1）/核因子-κB（NF-κB）信号通路与脑梗死后认知障碍风险及认知障碍程度的相关性。方法 选取2020年6月—2023年1月青海省人民医院收治的153例急性脑梗死患者，采用简易智力状态检查量表（MMSE）评估患者的认知功能，MMSE评分27～30分的患者作为认知正常组（86例）、MMSE评分≤ 26分的患者作为认知障碍组（67例）。比较两组蒙特利尔认知评估量表（MoCA）评分及MMSE评分；检测患者SIRT1、NF-κB mRNA相对表达量；采用Pearson法分析SIRT1、NF-κB mRNA相对表达量与MoCA评分和MMSE评分的相关性；绘制受试者工作特征（ROC）曲线，分析SIRT1、NF-κB mRNA相对表达量预测认知功能障碍的价值。结果 认知障碍组MMSE评分各项目得分及总分均低于认知正常组（P <0.05）。认知障碍组MoCA评分各项目得分及总分均低于认知正常组（P <0.05）。认知障碍组SIRT1 mRNA相对表达量低于认知正常组，NF-κB mRNA相对表达量高于认知正常组（P <0.05）。重度认知功能障碍患者SIRT1 mRNA相对表达量低于中度和轻度认知功能障碍患者（P <0.05），中度认知功能障碍患者低于轻度认知功能障碍患者（P <0.05），重度认知功能障碍患者NF-κB mRNA相对表达量高于中度和轻度认知功能障碍患者（P <0.05），中度认知功能障碍患者高于轻度认知功能障碍患者（P <0.05）。SIRT1 mRNA相对表达量与MoCA评分和MMSE评分呈正相关（r =0.497和0.532，均P <0.05），NF-κB mRNA相对表达量与MoCA评分和MMSE评分呈负相关（r =-0.518和-0.552，均P <0.05）。ROC曲线结果显示，SIRT1、NF-κB mRNA相对表达量单独及联合预测急性脑梗死认知功能障碍发生的曲线下面积分别为0.825（95% CI：0.749，0.901）、0.897（95% CI：0.826，0.968）、0.948（95% CI：0.916，0.980），敏感性分别为73.1%（95% CI：0.674，0.852）、83.6%（95% CI：0.788，0.949）、88.1%（95% CI：0.835，0.918），特异性分别为75.6%（95% CI：0.648，0.842）、80.2%（95% CI：0.755，0.916）、84.9%（95% CI：0.806，0.882）。结论 急性脑梗死后认知功能障碍患者SIRT1 mRNA相对表达量较低，NF-κB mRNA相对表达量较高，且表达量与认知功能障碍程度具有关，通过检测其表达可为预测急性脑梗死后认知功能障碍的发生提供帮助。

Abstract:

Objective To investigate the relationship between the silent mating-type information regulation 2 homologue 1 (SIRT1)/nuclear factor-kappa B (NF-κB) signaling pathway and the risk and severity of cognitive impairment.Methods A total of 153 patients with acute cerebral infarction admitted to Qinghai Provincial People's Hospital from June 2020 to January 2023 were selected, and their cognitive function was assessed by the Mini-Mental State Examination (MMSE) scale. Patients with MMSE score of 27-30 were included into the cognitive normal group (86 cases), and patients with MMSE score ≤ 26 were included into the cognitive impairment group (67 cases). Montreal Cognitive Assessment (MoCA) scores and MMSE scores were compared between the two groups. The relative mRNA expressions of SIRT1 and NF-κB were detected, and the Pearson correlation coefficient was used to analyze the correlations between the relative mRNA expressions of SIRT1 and NF-κB and the MoCA and MMSE scores. The receiver operating characteristic (ROC) curve was used to analyze the values of the relative mRNA expressions of SIRT1 and NF-κB in predicting the occurrence of cognitive impairment.Results The subitem and total scores of MMSE and MoCA in the cognitive impairment group were lower than those in the cognitive normal group (P < 0.05). Compared with the cognitive normal group, the relative mRNA expression of SIRT1 was lower and the relative mRNA expression of NF-κB was higher in the cognitive impairment group (P < 0.05). Patients with severe cognitive impairment had lower relative mRNA expression of SIRT1 than those with moderate and mild cognitive impairment (P < 0.05), and those with moderate cognitive impairment had lower relative mRNA expression of SIRT1 than those with mild cognitive impairment (P < 0.05). Patients with severe cognitive impairment had higher relative mRNA expression of NF-κB than those with moderate and mild cognitive impairment (P < 0.05), and those with moderate cognitive impairment had higher relative mRNA expression of NF-κB than those with mild cognitive impairment (P < 0.05). The relative mRNA expression of SIRT1 was positively correlated with MoCA and MMSE scores (r =0.497 and 0.532, both P < 0.05), and the relative mRNA expression of NF-κB was negatively correlated with MoCA and MMSE scores (r =-0.518 and -0.552, both P < 0.05). The ROC curve analysis showed that the areas under the curves (AUCs) of the relative mRNA expressions of SIRT1 and NF-κB individually and in combination for predicting the occurrence of cognitive impairment following acute cerebral infarction were 0.825 (95% CI: 0.749, 0.901), 0.897 (95% CI: 0.826, 0.968), and 0.948 (95% CI: 0.916, 0.980), with the sensitivities being 73.1% (95% CI: 0.674, 0.852), 83.6% (95% CI: 0.788, 0.949), and 88.1% (95% CI: 0.835, 0.918), and the specificities being 75.6% (95% CI: 0.648, 0.842), 80.2% (95% CI: 0.755, 0.916), and 84.9% (95% CI: 0.806, 0.882).Conclusions The relative mRNA expression of SIRT1 is low and that of NF-κB is high in patients with cognitive impairment following acute cerebral infarction, and they are significantly correlated with the severity of cognitive impairment. Detecting their expressions can assist in predicting the occurrence of cognitive impairment following acute cerebral infarction.