脑动静脉畸形部分栓塞术后血管组织增殖与凋亡的变化

doi:10.3877/cma.j.issn.2095-5782.2022.02.006

中华介入放射学电子杂志 ›› 2022, Vol. 10 ›› Issue (02) : 152 -157. doi: 10.3877/cma.j.issn.2095-5782.2022.02.006

基础研究

脑动静脉畸形部分栓塞术后血管组织增殖与凋亡的变化

郭德华¹, 贺迎坤¹^,^†(

), 白卫星¹, 何艳艳¹, 李天晓¹^,^†(

)

^1. 450003　河南郑州，郑州大学人民医院脑血管病科，河南省人民医院神经外科；河南省神经介入研发与应用工程研究中心，河南省脑血管介入创新工程技术研究中心

收稿日期:2021-12-03 出版日期:2022-05-25
通信作者: 贺迎坤, 李天晓
基金资助:
河南省医学科技攻关计划省部共建项目(SB201901068); 河南省科技厅科技攻关项目(192102310369)

Changes in proliferation and apoptosis of vascular tissue after partial embolization of cerebral arteriovenous malformations

Dehua Guo¹, Yingkun He¹^,^†(), Weixing Bai¹, Yanyan He¹, Tianxiao Li¹^,^†()

^1. Department of Cerebrovascular Disease, Zhengzhou University People's Hospital; Department of Neurosurgery, Henan Provincial People's Hospital; Henan Provincial Neurointerventional Engineering Research Center, Henan International Joint Laboratory of Cerebrovascular Disease, Henan Zhengzhou 450003, China

Received:2021-12-03 Published:2022-05-25
Corresponding author: Yingkun He, Tianxiao Li

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引用本文：

郭德华, 贺迎坤, 白卫星, 何艳艳, 李天晓. 脑动静脉畸形部分栓塞术后血管组织增殖与凋亡的变化[J/OL]. 中华介入放射学电子杂志, 2022, 10(02): 152-157.

Dehua Guo, Yingkun He, Weixing Bai, Yanyan He, Tianxiao Li. Changes in proliferation and apoptosis of vascular tissue after partial embolization of cerebral arteriovenous malformations[J/OL]. Chinese Journal of Interventional Radiology(Electronic Edition), 2022, 10(02): 152-157.

目的

研究脑动静脉畸形（BAVM）部分栓塞术后不同时间段内血管组织的增殖与凋亡情况。

方法

调取2018年6月—2021年1月我院神经外科切除的脑动静脉畸形（BAVM）标本32例，其中术前栓塞+手术切除标本24例，根据术前栓塞与手术切除的时间间隔分为短期组（间隔时间< 1 d）、中期组（1 d <间隔时间< 28 d）、远期组（间隔时间> 28 d），对照组为单纯外科手术切除BAVM标本8例。采用HE染色观察不同组别BAVM大体病理观差别，免疫组化检测VEGF、eNOS以及Caspase-3确定BAVM血管组织增殖与凋亡活性，免疫荧光检测CD31评估新生血管数量，TUNEL染色检测BAVM血管组织细胞凋亡数量。

结果

中期组BAVM的VEGF、eNOS及Caspase-3表达较其他各组均存在统计学差异（P < 0.05）；中期组BAVM新生血管数量、凋亡细胞数量较其他各组差异亦存在统计学意义（P < 0.05）。

结论

术前栓塞可引起BAVM血管组织的增殖与凋亡，这种增殖与凋亡现象与栓塞时间密切相关，在栓塞中期（1~28 d）表现最为明显，因此过长的手术间隔可能会增加患者的出血风险。

关键词: 脑动静脉畸形, 部分栓塞术, 细胞增殖, 细胞凋亡

Objective

To investigate the proliferation and apoptosis of vascular tissue in different time periods after partial embolization of brain arteriovenous malformation (BAVM).

Methods

A total of 32 BAVM specimens resected at the Department of Neurosurgery, Henan Provincial People's Hospital, from January 2018 to January 2021, including 24 preoperative embolization + surgical resection specimens, which were divided into short-term group (interval < 1 day), medium-term group (1 day < interval < 28 days), long-term group (interval > 28 days) according to the time interval between preoperative embolization and surgical resection.The control group consisted of 8 patients with BAVM specimens that were surgically removed alone. H E staining was used to observe the differences in the gross pathology of BAVM among different groups, immunohistochemical detection of VEGF, eNOS as well as caspase-3 was used to determine the proliferation and apoptotic activity of BAVM vascular tissues, immunofluorescence detection of CD31 was used to assess the number of neovessels, and TUNEL staining was used to detect the number of apoptosis in BAVM vascular tissues.

Results

The expressions of VEGF, eNOS, and Caspase-3 in BAVM was higher in the medium-term group compared with all other groups (P < 0.05); There were also significant differences in the number of neovessels and apoptotic cells of BAVM in the medium-term group compared with the other groups (P < 0.05).

Conclusions

Preoperative embolization can cause proliferation and apoptosis of BAVM vascular tissue, and such proliferation and apoptosis phenomenon was closely related to the embolization time, which was most obvious at the middle stage (1 day-28 days) of embolization.So a long interval between embolization and surgery may increase the risk of bleeding for the patients.

Key words: BAVM, Partial embolization, Cell proliferation, Apoptosis

表1 纳入病例的基线资料

组别	样本量（例）	出血史（例）		Spetzler-Martin分级（例）			年龄（±s，岁）	栓塞时长（m_0.5± IQR，d）
组别	样本量（例）	有	无	2级	3级	4级	年龄（±s，岁）	栓塞时长（m_0.5± IQR，d）
对照组	8	7	1	5	3	0	32.4±19.6	N
短期组	9	7	2	3	3	3	26.7±18.6	1
中期组	8	6	2	1	3	4	28.3±12.2	5.5±9.0
远期组	7	7	0	1	4	2	25.9±8.8	1 478±1 656.5
P值		0.720		0.240			0.915

表1 纳入病例的基线资料

组别	样本量（例）	出血史（例）		Spetzler-Martin分级（例）			年龄（±s，岁）	栓塞时长（m_0.5± IQR，d）
组别	样本量（例）	有	无	2级	3级	4级	年龄（±s，岁）	栓塞时长（m_0.5± IQR，d）
对照组	8	7	1	5	3	0	32.4±19.6	N
短期组	9	7	2	3	3	3	26.7±18.6	1
中期组	8	6	2	1	3	4	28.3±12.2	5.5±9.0
远期组	7	7	0	1	4	2	25.9±8.8	1 478±1 656.5
P值		0.720		0.240			0.915

图1 HE染色（×100）1A：对照组；1B：短期组；1C：中期组；1D：远期组。

图2 VEGFA、eNOS、Caspase-3免疫组化结果及半定量分析（×200）

图3 CD31免疫荧光（×200）（绿色为CD31，蓝色为细胞核DAPI染色）3A、3B:对照组、短期组，畸形血管周边新生血管鲜见；3C：中期组，红色箭头为BAVM畸形血管，白色箭头指示为新生血管组织；3D：远期组，白色箭头为已有成熟结构的小畸形血管；3E~3H：TUNEL染色（×200）；3I、3J：新生血管计数及TUNEL阳性细胞计数结果。

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