大鼠永久性大脑中动脉闭塞模型病理进程研究  

Pathological process of permanent middle cerebral artery occlusion model in rats

作　　者：宁珑 杨茜 孙航 许春萍 宋雪兰 颜明丽 何芳雁 NING Long;YANG Qian;SUN Hang;XU Chunping;SONG Xuelan;YAN Mingli;HE Fangyan(College of Traditional Chinese Medicine,Yunnan University of Chinese Medicine,Kunming 650500,China)

机构地区：[1]云南中医药大学中药学院,昆明650500

出　　处：《医学动物防制》2023年第6期594-600,共7页Journal of Medical Pest Control

基　　金：云南省科技厅-科技计划项目(202001AT070138);云南省科技厅-云南中医学院中医联合重点项目[2017FF117(-004)];云南省科技厅-云南中医学院中医联合青年项目[2018FF001(-074)];云南省科技厅-科技计划项目(202101AT070264)。

摘　　要：目的探究永久性大脑中动脉闭塞(permanent middle cerebral artery occlusion,pMCAO)大鼠模型病理进程,为缺血性脑卒中(ischemic stroke,IS)药效学给药时间窗提供依据。方法笔者于2020年12月—2021年12月进行研究,采用线栓法复制大鼠pMCAO模型,以神经学评分和脑血流量(cerebral blood flow,CBF)为纳入标准筛选出合格大鼠。于术后30min、3h、6h、24h、3d、7d、14d、21d、28d,以其行为学改变、脑组织病理学改变[苏木精-伊红(hematoxylineosin,HE)染色法]和神经元损伤(Nissl染色)为主要指标,探讨大鼠pMCAO模型病理进程分期。结果大鼠pMCAO模型:缺血30min~3h,开始出现神经功能缺损症状,但脑组织无明显病理性损伤,为超早期;缺血3~24h,脑组织出现轻微缺血灶,为急性期;缺血24h~3d,发生运动功能障碍、脑组织水肿、神经细胞开始死亡、炎性细胞(小胶质细胞,浆细胞)浸润,为坏死期;缺血3~7d,脑组织液化,神经细胞死亡,尼氏体减少,为恢复早期;缺血7~28d,神经功能缺损和运动功能障碍症状开始恢复,损伤侧液化坏死区周围胶质细胞增生,液化坏死神经细胞清除,为恢复后期。结论结合临床IS患者的病理特征和大鼠pMCAO模型的病理进程,得出IS药效学研究应以7d、14d、21d、28d为持续治疗时间。Objective To explore the pathological process of permanent middle cerebral artery occlusion(pMCAO)in a rat model to provide a basis for pharmacodynamics time window for ischemic stroke(IS).Methods From December 2020 to December 2021,the rat pMCAO model was replicated by suture-occluded method,and the rats were screened for eligibility by neurological score and cerebral blood flow(CBF)as inclusion criteria.At 30min,3h,6h,24h,3d,7d,14d,21d and 28d postoperatively,behavioral changes,brain histopathological changes(hematoxylin-eosin staining,HE)and neuronal damage(Nissl staining)were used as the main indexes to explore the stages of the pathological process in the rat pMCAO model.Results In the rat pMCAO model,symptoms of neurological deficits began to appear in 30min-3h of ischemia,but there was no obvious pathological damage to brain tissue,considered as ultra-early stage.In 3h-24h of ischemia,slight ischemic foci appeared in brain tissue,considered as acute stage.In 24h-3d of ischemia,motor dysfunction,brain tissue edema,neural cell death and inflammatory cell(microglia,plasma cells)infiltration occurred,considered as necrotic stage.In 3-7d of ischemia brain tissue liquefaction,neuronal cell death and neural cell reduction were observed in the early stage of recovery.In 7-28d of ischemia,the symptoms of neurological deficit and motor dysfunction began to recover,the glial cells around the liquefied necrotic area on the injury side proliferated and the liquefied necrotic nerve cells cleared in the late recovery stage.Conclusion In combination with the pathological characteristics of clinical IS patients and the pathological course of the rat pMCAO model,IS pharmacodynamic studies should be conducted with 7d,14d,21d and 28d as the duration of treatment.

关 键 词：缺血性脑卒中 pMCAO 模型稳定性 病理进程 行为学改变 病理学改变 大鼠 

分 类 号：R743.3[医药卫生—神经病学与精神病学]