血管性痴呆大鼠模型制作方法的改良

Improvement of the method to establish a rat model of vascular dementia

目的对血管性痴呆(VD)大鼠模型的造模方法进行改进,使血管性痴呆的实验研究更加科学可靠。方法采用"反复夹闭颈动脉加注射硝普钠降压再加单侧永久结扎颈总动脉法"制备VD大鼠模型,并用脑复康(吡拉西坦)加以模型验证。实验从大鼠行为学和组织病理两个方面评价VD模型。结果实验结果显示:对比假手术组,模型组大鼠定位航行潜伏期延长,空间搜索穿越平台次数减少,海马病理切片显示:细胞数量较少、细胞轮廓模糊皱缩、胞质深染、核不清晰;脑复康阳性药物对照组上述指标明显改善。结论硝普钠注射量为2.0 mg/kg时,手术室温控制在28℃且术后24 h内控制在25℃,大鼠状态稳定,死亡数减少;术中反复阻断三次双侧颈总动脉后直接永久性结扎左侧颈总动脉,可以切断大约三分之一的脑供血,造成慢性脑供血不足状态,更接近VD发病机制。

Objective To improve the method to establish a rat model of vascular dementia and to better serve the experimental studies on vascular dementia. Methods We used the method of＂repeatedly clipping the carotid artery combined with injection of sodium nitroprusside and with permanent unilateral carotid artery ligation＂to prepare a rat model of vascular dementia. The drug piracetam was used to validate the established rat model in respect of the behavior and histopathology. Results Different from the reports of previous research,firstly,the results of this study suggested that injection dose of sodium nitroprusside should be 2. 0 mg / kg,room temperature should be controlled at 28℃ during surgical operation,and kept at 25℃ postoperatively for 24 hours. Under these experimental conditions,the rats were stable and the death rate was reduced. Secondly,＂repeatedly clipping carotid artery combined with permanent unilateral carotid artery ligation＂could cut off about a third of cerebral blood supply,and causing chronic cerebral ischemia,which is seemingly more consistent with the pathogenesis of vascular dementia. Experimental results showed that compared with the control group,the navigation incubation period was extended and space search ability became worse in the model group,cell number was decreased,with blurred cell contour and deeply stained cytoplasm,and cell nuclei were not clear in the hippocampal tissue.Conclusions Our findings indicate that the improved method ＂ repeatedly clipping the carotid artery combined with injection of sodium nitroprusside and with permanent unilateral carotid artery ligation＂ can be used to efficiently establish a rat model of vascular dementia. The similar results of experiment using piracetam validate that this rat model can be used invascular dementia-related experimental studies.