肠内尼莫地平对蛛网膜下腔出血动物模型内皮细胞凋亡的影响。

The Impact of Enteral Nimodipine on Endothelial Cell Apoptosis in an Animal Subarachnoid Hemorrhage Model.

机构信息

Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Korea.

Department of Neurosurgery, Chungnam National University Sejong Hospital, Sejong, South Korea.

出版信息

Neurocrit Care. 2024 Oct;41(2):608-618. doi: 10.1007/s12028-024-01980-w. Epub 2024 Apr 8.

DOI:10.1007/s12028-024-01980-w

PMID:38589694

Abstract

BACKGROUND

Enteral nimodipine is the most evidence-based and widely used drug for the treatment of delayed cerebral ischemia and is known to have various neuroprotective functions. However, the neuroprotective mechanism of nimodipine still remains unclear, and the effects of nimodipine remain ambiguous. Herein, we studied the effect of enteral nimodipine on endothelial apoptosis after subarachnoid hemorrhage (SAH).

METHODS

SAH was experimentally introduced in white rabbits (n = 42) that were grouped as follows: enteral nimodipine (SAH-nimodipine group, n = 14), a control that received normal saline (SAH-saline group, n = 13), and a control without hemorrhage (control group, n = 15). On the third day after SAH induction, the brain stem, including the vertebrobasilar vascular system, was extracted. The effects of enteral nimodipine were analyzed by group using histopathologic analysis, including immunohistochemical staining of apoptosis-related proteins (Bcl2 [anti-apoptotic] and Bax [pro-apoptotic]).

RESULTS

Cytoplasmic vacuolation of smooth muscle cells was observed in two SAH hemorrhagic groups and was more prominent in the SAH-saline group. Endothelial desquamation was observed only in the SAH-saline group. For the basilar artery, expression of Bcl2 and Bax in the SAH-nimodipine group was lower than that in the SAH-saline group, but significant differences were not observed (p = 0.311 and p = 0.720, respectively). In penetrated arterioles, the expression of Bax in the SAH-nimodipine group was significantly lower than that of the SAH-saline group (p < 0.001). The thickness of the tunica media in the basilar artery was thinner in the SAH-nimodipine group than in the SAH-saline group (p < 0.001).

CONCLUSIONS

This study suggests that enteral nimodipine may have a neuroprotective function by inhibiting endothelial apoptosis in small arterioles and preventing smooth muscle cell proliferation in large arteries.

摘要

背景

肠内尼莫地平是治疗迟发性脑缺血最有循证医学证据和应用最广泛的药物，已知具有多种神经保护功能。然而，尼莫地平的神经保护机制仍不清楚，其作用仍存在争议。在此，我们研究了肠内尼莫地平对蛛网膜下腔出血（SAH）后内皮细胞凋亡的影响。

方法

采用实验性方法在白兔（n=42）中诱导 SAH，分组如下：肠内尼莫地平（SAH-尼莫地平组，n=14）、接受生理盐水的对照组（SAH-生理盐水组，n=13）和无出血的对照组（n=15）。在 SAH 诱导后的第三天，提取包括椎基底血管系统在内的脑干。采用组间比较的方法，通过组织病理学分析，包括凋亡相关蛋白（Bcl2[抗凋亡]和 Bax[促凋亡]）的免疫组织化学染色，分析肠内尼莫地平的作用。

结果

两个 SAH 出血组均观察到平滑肌细胞胞质空泡化，SAH-生理盐水组更为明显。仅在 SAH-生理盐水组观察到内皮细胞脱落。对于基底动脉，SAH-尼莫地平组的 Bcl2 和 Bax 表达均低于 SAH-生理盐水组，但差异无统计学意义（p=0.311 和 p=0.720）。在穿透性小动脉中，SAH-尼莫地平组 Bax 的表达明显低于 SAH-生理盐水组（p<0.001）。SAH-尼莫地平组基底动脉中膜厚度较 SAH-生理盐水组薄（p<0.001）。