眶上锁孔入路手术建立食蟹猴大脑中动脉闭塞模型

doi:10.3877/cma.j.issn.2095-123X.2024.01.002

目的

应用眶上锁孔入路手术方法建立食蟹猴大脑中动脉闭塞(MCAO)模型并评价模型制作效果。

方法

4只普通级实验猴随机分为2组，手术组3只实验猴经左侧眶上锁孔入路手术开颅，显露并电凝切断左侧大脑中动脉M1段起始部，建立MCAO模型；对照组1只实验猴经左侧眶上锁孔入路手术开颅，仅显露左侧大脑中动脉M1段起始部，不电凝切断，作为阴性对照。分别于术后24 h、3 d、7 d、14 d、28 d对所有实验猴行非人灵长类动物卒中量表（NHPSS）评分，于术后7 d对所有实验猴行头颅MRI轴位T2加权扫描。

结果

所有实验猴术后无死亡，无明显术后并发症，实验周期内均存活良好。手术组实验猴术后24 h、3 d、7 d、14 d、28 d的NHPSS评分分别为（19.67±1.15）、（22.00±1.00）、（19.33±1.15）、（18.67±1.53）、（18.00±1.00）分。对照组实验猴术后24 h、3 d、7 d、14 d、28 d的NHPSS评分均为0分。头颅MRI轴位T2WI提示：手术组实验猴左侧大脑中动脉支配区域脑组织均出现梗死灶，分布于左侧额叶、顶叶、颞叶及基底节区的部分区域，伴有轻度脑水肿；对照组实验猴脑内无梗死灶及脑水肿形成。

结论

应用眶上锁孔入路手术方法造模具备微创优势，模型效果可靠，重复性好，适合进行食蟹猴MCAO模型的批量制作。

关键词: 大脑中动脉闭塞, 眶上, 锁孔入路, 食蟹猴, 动物模型

Objective

To evaluate the effectiveness of building cynomolgus monkey middle cerebral artery occlusion (MCAO) model by taking supraorbital keyhole approach operation.

Methods

Four ordinary grade experimental monkeys were randomly divided into two groups. Three experimental monkeys of operation group underwent left supraorbital keyhole approach craniotomy, initial part of M1 segment of left middle cerebral artery was exposed and then coagulated and cut to make MCAO model. One experimental monkey of control group underwent left supraorbital keyhole approach craniotomy, initial part of M1 segment of left middle cerebral artery was exposed but not coagulated and cut to make negative control. All experimental monkeys were evaluated using the non-human primate stroke scale (NHPSS) at 24 h, 3 d, 7 d, 14 d, and 28 d postoperatively. Brain MRI axial T2 weighted scans were performed on all experimental monkeys at 7 d postoperatively.

Results

All experimental monkeys survived after operation without any significant postoperative complications, and lived well during experimental period. The NHPSS scores of the operation group at postoperative time of 24 h, 3 d, 7 d, 14 d, 28 d was (19.67±1.15), (22.00±1.00), (19.33±1.15), (18.67±1.53), (18.00±1.00) points respectively. The NHPSS scores of the control group at postoperative time of 24 h, 3 d, 7 d, 14 d, 28 d were all 0 points. Brain MRI axial T2 weighted scan at 7 d after operation showed that brain infarction focus appeared in the blood supply area of left middle cerebral artery of all experimental monkeys of operation group, scattered in the left frontal lobe, parietal lobe, temporal lobe and basal ganglion area, and accompanied with mild cerebral edema, whereas no brain infarction focus and brain edema was appeared in the experimental monkey of control group.

Conclusion

The application of the supraorbital keyhole approach surgical method has the advantage of minimally invasion, reliable model effect, good repeatability. The approach method has good repeatability and can make mass production of cynomolgus monkey MCAO models.

Key words: Middle cerebral artery occlusion, Supraorbital, Keyhole approach, Cynomolgus monkey, Animal model

图1 眶上锁孔入路手术建立食蟹猴MCAO模型手术过程图A：左侧眶上小骨窗开颅；B：切开硬膜暴露前额叶；C：显露左侧颈内动脉分叉部；D：显露左侧MCA M1段起始部；E：电凝并切断左侧MCA M1段起始部；F：关颅前所示锁孔状术区，额叶保护完好；MCAO：大脑中动脉闭塞；ACA：左侧大脑前动脉；ACP：左侧前床突；AFV：左侧额叶前静脉；CNⅡ：左侧视神经；CNⅢ：左侧动眼神经；DI：左侧MCA M1段起始部闭塞远端；FL：额叶；ICA：左侧颈内动脉；M1：左侧MCA M1段起始部；MCA：左侧MCA；PI：左侧MCA M1段起始部闭塞近端

Fig.1 Image of operation procedure by taking supraorbital keyhole approach to build cynomolgus MCAO model

图2 手术组实验猴术后NHPSS评分结果

Fig.2 Postoperational NHPSS score of experimental monkey in operation group

图3 术后7 d实验猴头颅MRI轴位T2WI资料A：手术组实验猴左侧额顶叶梗死灶（星号所示）伴轻度水肿，T2WI呈高信号；B：手术组实验猴左侧颞叶、基底节区梗死灶（星号所示）伴轻度水肿，T2WI呈高信号；C：手术组实验猴左侧颞叶底部梗死灶（星号所示）伴轻度水肿，T2WI呈高信号；D~F：对照组实验猴脑内无梗死灶及水肿灶形成

Fig.3 Experimental monkey brain MRI axial T2 weighted image at 7 d after operation

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Taking supraorbital keyhole approach operation to build cynomolgus monkey middle cerebral artery occlusion model

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Taking supraorbital keyhole approach operation to build cynomolgus monkey middle cerebral artery occlusion model