孙伟, 耿悦, 陈叶婷, 唐小杭, 张永杰, 顾胜华, 谢家骏, 张泽安, 田雪松*
本文旨在研究Sprague-Dawley (SD)与Wistar大鼠双侧颈总动脉结扎(bilateral common carotid artery occlusion, BCCAO)后的大脑病理变化及认知功能差异。雄性SD和Wistar大鼠分别随机分为2组：假手术(S-sham和W-sham)组与手术(S-BCCAO和W-BCCAO)组。BCCAO术后1、3、7、14及28 d，观察各组存活率及瞳孔对光反射(pupillary light reflex, PLR)消失率；术后28 d行明暗箱、Y迷宫及新气味识别测试，检测大鼠认知功能；用HE和Luxol fast blue染色法观察灰质(海马)、白质(视束)、视神经和视网膜的病理改变。结果显示，W-BCCAO组大鼠的存活率为62.5%，PLR全部消失；S-BCCAO组大鼠的存活率100%，PLR消失率为58.3%。和各自的假手术组相比，W-BCCAO组大鼠在明箱的滞留时间及活动距离比例均显著增加，S-BCCAO组大鼠则无明显变化；S-BCCAO组大鼠在Y迷宫III臂(迷宫臂)的滞留时间及活动距离比例均显著减少，而W-BCCAO组大鼠无明显变化；S-BCCAO组大鼠的新气味辨识比率显著降低，而W-BCCAO组大鼠无明显变化。S-BCCAO组大鼠海马CA1区可见缺血性损伤，而W-BCCAO组无明显损伤；S-BCCAO及W-BCCAO组大鼠均可见视束、视神经缺血性损伤；S-BCCAO、W-BCCAO大鼠视网膜损伤明显，总厚度明显变薄，其中S-BCCAO组大鼠可见节细胞层(ganglion cell layer, GCL)、内网层(inner plexiform layer, IPL)及外网层(outer plexiform layer, OPL)变薄，其它各层与S-sham组相比无显著差异，W-BCCAO组大鼠除外核层(outer nuclear layer, ONL)外，其余各层与W-sham组相比均变薄。上述结果表明，SD和Wistar大鼠BCCAO术后海马和视觉传导通路病理变化存在差异，学习记忆损伤程度也有所不同，提示应根据研究目的选择不同品系大鼠建立血管性痴呆模型。
Differences of brain pathological changes and cognitive function after bilateral common carotid artery occlusion between Sprague-Dawley and Wistar rats
SUN Wei, GENG Yue, CHEN Ye-Ting, TANG Xiao-Hang, ZHANG Yong-Jie, GU Sheng-Hua, XIE Jia-Jun, ZHANG Ze-An, TIAN Xue-Song*
Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
The aim of the present study was to investigate the differences of the pathological changes and cognitive function after
bilateral common carotid artery occlusion (BCCAO) between Sprague-Dawley (SD) and Wistar rats. Male SD and Wistar rats were randomly divided into 2 groups, respectively: sham operated (S-sham and W-sham) and operated (S-BCCAO and W-BCCAO) groups. The survival rate and the rate of loss of pupillary light reflex (PLR) were observed on day 1, 3, 7, 14 and 28 after the operation, and the light-dark box, Y-maze and odor recognition tests were performed to detect cognitive function on day 28 after the operation. HE and Luxol fast blue staining were used to observe the pathological changes of gray matter (hippocampus), white matter (optical tract), optic nerve, and retina. The results showed that the survival rate of the W-BCCAO group was 62.5%, and PLR loss rate was 100%; whereas the survival rate of the S-BCCAO group was 100%, and PLR loss rate was 58.3%. In the W-BCCAO group, percentages of time spent and distance traveled in the light box of were more than those in the W-sham group, but there was no statistical significance between the S-BCCAO and S-sham groups. In the S-BCCAO group, the percentages of time spent and distance traveled in the III arm (labyrinth arm) of the Y-maze were less than those in the S-sham group, but no statistical significance was found between the W-BCCAO group and W-sham group. In the S-BCCAO group, the discrimination ratio of the odor recognition task was less than that in the S-sham group, but no statistical significance could be seen between the W-BCCAO and W-sham groups. Ischemic injury was observed in the CA1 area of the hippocampus in the S-BCCAO group, but no readily visible damage was observed in the W-BCCAO group. Ischemic injury of the visual beam and optic nerve was observed in both the S-BCCAO and W-BCCAO groups. Compared with the corresponding sham groups, the S-BCCAO and W-BCCAO groups showed serious retinal damage with significant thinner retina. The ganglion cell layer (GCL), inner plexiform layer (IPL), and outer plexiform layer (OPL) were thinner in the S-BCCAO group, but no statistical significances were shown in the other layers. All the layers, except the outer nuclear layer (ONL), were significantly thinner in the W-BCCAO group. The results indicate that there are differences of the pathological changes in the hippocampus and visual conduction pathway after BCCAO between SD and Wistar rats, and the degree of learning and memory injury was also different, which suggests that the vascular dementia model of different rat strains should be selected according to research purpose.
通讯作者：田雪松 E-mail: firstname.lastname@example.org
孙伟, 耿悦, 陈叶婷, 唐小杭, 张永杰, 顾胜华, 谢家骏, 张泽安, 田雪松. Sprague-Dawley与Wistar大鼠双侧颈总动脉结扎后大脑病理变化和认知功能的差异[J]. 生理学报 2019; 71 (5): 705-716.
SUN Wei, GENG Yue, CHEN Ye-Ting, TANG Xiao-Hang, ZHANG Yong-Jie, GU Sheng-Hua, XIE Jia-Jun, ZHANG Ze-An, TIAN Xue-Song. Differences of brain pathological changes and cognitive function after bilateral common carotid artery occlusion between Sprague-Dawley and Wistar rats. Acta Physiol Sin 2019; 71 (5): 705-716 (in Chinese with English abstract).