Relationship between TGF-β/Smads Signaling Pathway and Cognitive Dysfunction in Patients with Aneurysmal Subarachnoid Hemorrhage
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摘要:
目的 探讨动脉瘤性蛛网膜下腔出血(aneurysmal subarachnoid hemorrhage,aSAH)患者外周血内转化生长因子β(transforming growth factor β,TGF-β)/苏氨酸激酶受体(aerine-threonine kinase receptors,Smads)信号转导通路相关因子与认知功能障碍的关系。 方法 回顾性选取2018年10月至2022年3月崇左市人民医院收治的100例aSAH患者的临床资料,根据患者蒙特利尔认知评估量表(montreal cognitive assessment scale,MoCA)评分分组,其中存在认知功能障碍54例,无认知功能障碍46例。比较2组临床资料、外周血TGF-β、Smad1、Smad3及Smad7 mRNA表达水平;多因素分析通路相关因子与aSAH患者认知功能障碍的关系;采用受试者工作特征曲线(receiver operating characteristic,ROC)评估通路相关因子对aSAH患者认知功能障碍的预测价值。 结果 认知功能障碍组患者外周血TGF-β、Smad1、Smad3、Smad7 mRNA表达水平较无认知功能障碍组高(P < 0.05);多因素显示,通路相关因子与aSAH患者认知功能障碍显著相关(P < 0.05);ROC显示,通路相关因子联合预测aSAH患者认知功能障碍的曲线下面积(area under the curve,AUC)优于单独预测(P < 0.05)。 结论 aSAH患者外周血内TGF-β/Smads信号转导通路相关因子高表达,提示该通路可能与患者认知功能障碍有关。 -
关键词:
- 动脉瘤性蛛网膜下腔出血 /
- TGF-β/Smads信号转导通路 /
- 认知功能障碍
Abstract:Objective To investigate the relationship between factors related to the transforming growth factor β(TGF-β)/Aerine-threonine kinase receptors(Smads) signaling pathway and cognitive dysfunction in peripheral blood of patients with aneurysmal subarachnoid hemorrhage(aSAH). Methods The clinical data of 100 patients with aSAH admitted to Chongzuo City People's Hospital from October 2018 to March 2022 were retrospectively selected and grouped according to the patients' Montreal Cognitive Assessment Scale(MoCA) scores, including 54 cases with cognitive dysfunction and 46 cases without cognitive dysfunction. The clinical data, peripheral blood TGF-β, Smad1, Smad3, and Smad7 mRNA expression levels of the two groups were compared. The relationship between pathway-related factors and cognitive dysfunction in patients with aSAH was analyzed in a multifactorial manner. The predictive value of pathway-related factors for cognitive dysfunction in aSAH patients was assessed using the receiver operating characteristic(ROC) curve. Results Peripheral blood TGF-β, Smad1, Smad3, and Smad7 mRNA expression levels were higher in the cognitively impaired group than in the group without cognitive impairment(P < 0.05). Multifactorial showed that pathway-related factors were significantly associated with cognitive impairment in patients with aSAH(P < 0.05). The ROC showed that the area under the curve(AUC) of pathway-related factors jointly predicted cognitive dysfunction in patients with aSAH was superior to that predicted alone(P < 0.05). Conclusion The high expression of factors related to the TGF-β/Smads signaling pathway in the peripheral blood of aSAH patients suggests that this pathway may be associated with cognitive dysfunction in patients. -
表 1 引物序列
Table 1. Primer sequences
基因 引物 TGF-β mRNA 上游:5'-GACACCAACTACTGCTTCA-3' 下游:5'-ATCCAGGCTCCAGATGTAA-3' Smad1 mRNA 上游:5′-ATGAATGTGACCAGCTTGTTT-3′ 下游:5′-CTGCTTGGAACCAAATGGGAA-3′ Smad3 mRNA 上游:5′-GGGCCTACTGTCCAATGTCA-3′ 下游:5′-CCCAATGTGTCGCCTTGTA-3′ Smad7 mRNA 上游:5′-GGCCGGATCTCAGGCATTC-3′ 下游:5′-TTGGGTATCTGGAGTAAGGAGG-3′ GAPDH 上游:5′-CCTGCCAAGTATGATGAGAT-3′ 下游:5′-AGTGTCGCTGTTGAAGTC -3′ 表 2 2组临床资料比较[($\bar x \pm s $)/n(%)](1)
Table 2. Comparison of clinical data between the two groups[($\bar x \pm s $)/n(%)](1)
组别 n 性别(男) 年龄(岁) 受教育年限(a) 动脉瘤大小(mm) 糖尿病 高血压 烟酒史 并发症 认知功能障碍 54 30(55.56) 54.59 ± 10.62 6.59 ± 4.51 6.39 ± 1.25 7(12.96) 16(29.63) 12(22.22) 6(11.11) 无认知功能障碍 46 27(58.70) 53.29 ± 12.83 7.04 ± 4.68 6.58 ± 1.39 3(6.52) 10(21.74) 7(15.22) 2(4.35) t/χ2 0.100 0.554 0.489 0.719 0.541 0.804 0.392 0.762 P 0.752 0.581 0.626 0.474 0.462 0.370 0.374 0.383 表 3 2组TGF-β/Smads信号转导通路相关因子表达比较($\bar x \pm s $)
Table 3. Comparison of expression of factors related to TGF-β/Smads signaling pathway between the two groups ($\bar x \pm s $)
组别 n TGF-β mRNA Smad1 mRNA Smad3 mRNA Smad7 mRNA 认知功能障碍 54 0.58 ± 0.12 0.47 ± 0.08 0.50 ± 0.14 0.60 ± 0.17 无认知功能障碍 46 0.40 ± 0.09 0.32 ± 0.07 0.36 ± 0.09 0.45 ± 0.11 t 8.363 9.982 5.831 5.136 P < 0.001* < 0.001* < 0.001* < 0.001* *P < 0.05。 表 4 赋值量表
Table 4. Assignment Scale
因素 赋值情况 TGF-β mRNA 连续变量,按照实测值 Smad1 mRNA 连续变量,按照实测值 Smad3 mRNA 连续变量,按照实测值 Smad7 mRNA 连续变量,按照实测值 表 5 TGF-β/Smads信号转导通路相关因子与aSAH患者认知功能障碍的关系
Table 5. Relationship between factors related to TGF-β/Smads signaling pathway and cognitive dysfunction in patients with aSAH
因素 β S.E. Waldχ2 OR 95%CI P TGF-β mRNA 2.726 0.512 28.351 15.274 5.142~45.372 < 0.001* Smad1 mRNA 2.682 0.422 40.391 14.614 3.874~55.129 < 0.001* Smad3 mRNA 2.691 0.389 47.868 14.752 4.115~52.884 < 0.001* Smad7 mRNA 2.736 0.401 46.551 15.425 3.967~59.974 < 0.001* *P < 0.05。 表 6 TGF-β/Smads信号转导通路相关因子预测aSAH患者认知功能障碍的ROC分析
Table 6. ROC analysis of TGF-β/Smad ssignaling pathway-related factors to predict cognitive dysfunction in patients with aSAH
指标 AUC 95%CI Z统计 截断值 敏感度/(%) 特异度/(%) P TGF-β mRNA 0.704 0.604~0.791 3.905 > 0.51 59.26 78.26 < 0.001* Smad1 mRNA 0.817 0.727~0.887 7.483 > 0.47 62.96 89.13 < 0.001* Smad3 mRNA 0.738 0.641~0.821 4.711 > 0.44 64.81 78.26 < 0.001* Smad7 mRNA 0.706 0.607~0.793 3.972 > 0.51 61.11 73.91 < 0.001* 联合预测 0.918 0.846~0.964 16.150 75.93 91.30 < 0.001* *P < 0.05。 表 7 TGF-β/Smads信号转导通路相关因子联合与单独预测方案预测价值比较
Table 7. Comparison of predictive value of TGF-β/Smads signaling pathway-related factors in combination with separate prediction schemes
预测方案 面积之差 标准误差 Z统计 95%CI P 联合VS TGF-β 0.215 0.059 3.716 0.101~0.328 < 0.001* 联合VS Smad1 mRNA 0.101 0.049 2.076 0.006~0.197 0.038* 联合VS Smad3 mRNA 0.180 0.055 3.298 0.073~0.287 0.001* 联合VS Smad7 mRNA 0.212 0.058 3.631 0.098~0.326 < 0.001* *P < 0.05。 表 2 2组临床资料比较[($\bar x \pm s $)/n(%)](2)
Table 2. Comparison of clinical data between the two groups[($\bar x \pm s $)/n(%)](2)
组别 n Hunt-Hess分级 改良FISHER分级 动脉瘤位置 治疗方式 1~2级 3~4级 1~2级 3~4级 前循环 后循环 夹闭 栓塞 认知功能障碍 54 44(81.48) 10(18.52) 36(66.67) 18(33.33) 47(87.04) 7(12.96) 23(42.59) 31(57.41) 无认知功能障碍 46 42(91.30) 4(8.70) 35(76.09) 11(23.91) 40(86.96) 6(13.04) 20(43.48) 26(56.52) t/χ2 1.991 1.071 0.000 0.008 P 0.158 0.301 0.991 0.929 表 2 2组临床资料比较[($\bar x \pm s $)/n(%)](3)
Table 2. Comparison of clinical data between the two groups[($\bar x \pm s $)/n(%)](3)
组别 n 术后血性脑脊液引流方式 腰大池持续引流 反复腰穿 认知功能障碍 54 24(44.44) 30(55.56) 无认知功能障碍 46 29(43.04) 17(36.96) t/χ2 3.450 P 0.063 -
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