血管性痴呆动物模型研究概述

Overview of the Animal Model of Vascular Dementia

对近年来采用不同方法复制的血管性痴呆动物模型进行比较分析。血管性痴呆模型的复制动物主要采用大鼠和C57BL/6品系小鼠。根据模型复制的病理机制可将血管性痴呆动物模型分为慢性脑低灌注动物模型、慢性脑低灌注混合模型、局灶性脑缺血动物模型、缺血再灌注动物模型。慢性脑低灌注动物模型的复制方法有两血管阻断法(2-VO)及改良2-VO、两血管渐进闭塞法(2VGO)、两血管狭窄法(BCAS);慢性脑低灌注混合模型的复制方法有2-VO+腹腔注射硝普钠、2-VO+尾动脉放血、2-VO+β淀粉样蛋白1-42(Aβ1-42)脑室内注射、改良2-VO+双肾双夹法(2K2C);局灶性脑缺血动物模型的复制方法有大脑中动脉梗死法(线栓法、电凝法)、多发性脑梗死栓塞法(如四氧化三铁颅外吸附法);缺血再灌注动物模型的复制方法有大脑中动脉线栓法、结扎法等。血管性痴呆动物模型因制备方法的不同,其病理组织学改变和认知功能损害程度也有所不同,研究者需根据血管性痴呆的亚型和研究目标做出相应的选择。

In this article,we compared and analyzed the vascular dementia animal models replicated by different methods in recent years.The vascular dementia model was mainly replicated in rats and C57BL/6 mice.According to the pathological mechanism of model replication,vascular dementia animal model can be divided into chronic global cerebral hypoperfusion animal model,chronic cerebral hypoperfusion mixed model,focal cerebral ischemia animal model,and ischemia reperfusion animal model.The replication methods of chronic cerebral hypoperfusion animal model include two-vessel occlusion method(2-VO)and modified 2-VO,two-vessel gradual occlusion method(2VGO),and bilateral carotid artery stenosis method(BCAS).The mixed model of chronic cerebral hypoperfusion can be established by the methods of 2-VO+intraperitoneal injection of sodium nitropropone,2-VO+caudal arterial blood-letting,2-VO+intraventricular injection ofβ-amyloid 1-42(Aβ1-42),and modified 2-VO+two-kidney two-clip method(2K2C).The replication methods of animal model of focal cerebral ischemia include middle cerebral artery infarction(by suture-occlusion or electrocoagulation)and multiple cerebral infarction embolization(e.g.,ferric oxide extracranial adsorption).Middle cerebral artery sutureocclusion and ligation can be used to replicate the animal model of ischemia reperfusion.The various preparation methods can lead to the differences in the histopathological changes and cognitive impairment of vascular dementia animal models.Therefore,researchers should make corresponding choices according to the subtypes and research objective of vascular dementia.