ω-agatoxin-ⅣA对猴脑缺血模型的神经保护作用

The neuro-protective effect ofω-agatoxin-ⅣA:an experimental study in monkey models of middle cerebral artery ischemia

目的探讨P/Q型钙离子通道拮抗剂ω-agatoxin-IVA(蜘蛛毒提取物)在猴脑缺血模型中的神经保护作用。方法成年广西猕猴8只,随机分成治疗组和对照组,每组4只。术前CT平扫和血管造影排除脑血管及颅内病变。各组动物经介入法插管至大脑中动脉,注入白体血栓造成大脑中动脉血栓栓塞,数字减影血管造影(DSA)证明栓塞成功,于术后30 min椎管内注射ω-agatoxin-IVA溶液,术后60 min行CT灌注扫描(CTP)观察梗死范围,术后1、15和30 d观察行为学表现,术后第30天行MRI扫描测量梗死体积,处死动物并取脑组织行HE染色,观察病理改变。结果术后介入血管造影和CTP均证明栓塞成功,术后60 min两组动物脑缺血范围在CTP图像上差异无统计学意义(P>0.05)。术后15和30 d行为学评分,治疗组分别为27.0±3.0和27.0±3.0,明显高于对照组的16.5±4.7和17.5±4.1,两组间差异有统计学意义(P<0.05)。术后30 d MRI扫描测量的梗死范围,治疗组明显低于对照组,两组间差异有统计学意义(64±38比193±24,P<0.05)。结论ω-agatoxin-IVA可以降低猴脑缺血后的梗死范围,减少神经功能损伤。

Objective To investigate the neuro-protective effect of ω-agatoxin-ⅣA in monkey models of middle cerebral artery ischemia. Methods A total of 8 adult monkeys were randomly and equally divided into treatment group （n = 4） and control group （n = 4）. Before the experimental procedure, plain CT scanning and angiography were performed in all monkeys to exclude any cerebral vascular or intraeranial disorders. Middle cerebral artery catheterization was completed in each animal, which was followed by the injection of monkey autologous blood clots to make the embolization, and subsequent DSA was employed to verify that the middle cerebral artery was really occluded. Intracanal injection of ω-agatoxin-ⅣA solution was carried out 30 minutes after the embolization. Cerebral blood flow （CBF） was determined by CT perfusion （CTP） scanning performed 60 minutes after the embolization to observe the infarction extent. Behavioral test was studied at 1, 15 and 30 days separately after the procedure. Thirty days after the treatment, MRI scan was employed to measure the infarction volume. Then the animals were sacrificed, and the brain tissues were collected and sent for pathologic study by using H＆E staining. Results Successful embolization of middle cerebral artery was achieved in all animals, which was confirmed by both DSA and CTP. At 60 minutes after the treatment, the difference in isehemie extent, that was estimated on CTP pictures, between the two groupswas not significant （P 〉 0.05）. The behavior test scores at 15 and 30 days in treatment group were 27.0 ± 3.0 and 27.0 ± 3.0 respectively, which were significantly higher than those incontrol group （16.5 ± 4.7 and 17.5 ± 4.1 respectively） with P 〈 0.05. MRI scanning_performed at 30 days after the treatment showed that the infarction extent in the treatment group was 64 ± 38, which was significantly lower than that in the control group （ 193 ± 24） with P 〈 0.05. Conclusion Intracanal injection of to-agatoxin-ⅣA solution employed soon after the cerebral infarction can reduce the infarction size and relieve neurological deficit in monkey models of middle cerebral artery ischemia.