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线粒体Omi/HtrA2信号通路参与脑出血患者的神经元凋亡。

Mitochondrial Omi/HtrA2 signaling pathway is involved in neuronal apoptosis in patients with cerebral hemorrhage.

作者信息

Tao Junqiang, Qi Shun, Wang Zhenxin, Dong Shanshan

机构信息

Neurosurgery, Yuhuan Second People's Hospital Yuhuan 317605, Zhejiang, China.

ICU, Taizhou Traditional Chinese Medicine Hospital Taizhou 317700, Zhejiang, China.

出版信息

Am J Transl Res. 2023 Jun 15;15(6):4033-4044. eCollection 2023.

Abstract

OBJECTIVE

This study aimed to analyze the role of mitochondrial Omi/HtrA2 signaling pathway in neuronal apoptosis in patients with cerebral hemorrhage (CH).

METHODS

In this retrospective analysis, the clinical data of 60 patients with CH who received craniotomy or minimally invasive intracranial hematoma (MIIH) were included in the case group, which was sub-divided into a craniotomy group (n=22) and a minimally invasive group (n=38) depending on the type of surgery. The brain tissue specimens of the above patients were retained in the surgical specimen repository of Yuhuan Second People's Hospital. Another 15 normal brain tissue samples retained in the surgical specimen repository were included in the normal group. The expression levels of Omi/HtrA2, X-linked inhibitor of apoptosis protein (XIAP), poly-adenosine diphosphate-ribose polymerase (PARP), pro-caspase 3, and pro-caspase 9 were determined using Western blotting.

RESULTS

The case group exhibited a higher proportion of neuronal apoptosis, higher expression levels of Omi/HtrA2, PARP, and pro-caspase 3 and 9, higher activities of caspase 3 and caspase 9 ( < 0.05), and lower XIAP expression ( < 0.05) in brain tissue than the normal group. The proportion of neuronal cell apoptosis in brain tissues was positively correlated with the expression of Omi/HtrA2, PARP, and pro-caspase 3 and pro-caspase 9 ( > 0, < 0.05), and the activity of caspase 3 and caspase 9 was negatively correlated with XIAP expression ( < 0, < 0.05). Compared with the craniotomy group, the minimally invasive group demonstrated higher efficacy and hematoma removal rate, shorter hematoma removal time, hematoma drainage time, operation time, and hospital stay, less intraoperative bleeding, and lower postoperative complication rates ( < 0.05). The minimally invasive group showed higher expression level of serum XIAP and lower levels of serum caspase 3 and caspase 9 than the craniotomy group ( < 0.05).

CONCLUSIONS

Mitochondrial Omi/HtrA2 signaling pathway may be involved in neuronal apoptosis. MIIH has the advantages of high efficacy, high hematoma clearance rate, and few complications for the treatment of CH.

摘要

目的

本研究旨在分析线粒体Omi/HtrA2信号通路在脑出血(CH)患者神经元凋亡中的作用。

方法

在这项回顾性分析中,将60例行开颅手术或微创颅内血肿清除术(MIIH)的CH患者的临床资料纳入病例组,根据手术类型将其分为开颅手术组(n = 22)和微创组(n = 38)。上述患者的脑组织标本保存在玉环市第二人民医院手术标本库中。将保存在手术标本库中的另外15份正常脑组织样本纳入正常组。采用蛋白质印迹法检测Omi/HtrA2、X连锁凋亡抑制蛋白(XIAP)、聚腺苷二磷酸核糖聚合酶(PARP)、前半胱天冬酶-3和前半胱天冬酶-9的表达水平。

结果

与正常组相比,病例组脑组织中神经元凋亡比例更高,Omi/HtrA2、PARP、前半胱天冬酶-3和前半胱天冬酶-9的表达水平更高,半胱天冬酶-3和半胱天冬酶-9的活性更高(P < 0.05),XIAP表达更低(P < 0.05)。脑组织中神经元细胞凋亡比例与Omi/HtrA2、PARP、前半胱天冬酶-3和前半胱天冬酶-9的表达呈正相关(r > 0,P < 0.05),半胱天冬酶-3和半胱天冬酶-9的活性与XIAP表达呈负相关(r < 0,P < 0.05)。与开颅手术组相比,微创组疗效和血肿清除率更高,血肿清除时间、血肿引流时间、手术时间和住院时间更短,术中出血更少,术后并发症发生率更低(P < 0.05)。微创组血清XIAP表达水平高于开颅手术组,血清半胱天冬酶-3和半胱天冬酶-9水平低于开颅手术组(P < 0.05)。

结论

线粒体Omi/HtrA2信号通路可能参与神经元凋亡。MIIH治疗CH具有疗效高、血肿清除率高、并发症少等优点。

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