实验动物与比较医学 ›› 2020, Vol. 40 ›› Issue (6): 470-476.DOI: 10.3969/j.issn.1674-5817.2020.06.002

• 论著 • 上一篇    下一篇

双侧颈总动脉结扎致大鼠脑血流低灌注不同时程的神经功能障碍和病理学变化

孙成成1, 刘剑刚1#, 刘美霞1#, 李浩1, 罗增刚2   

  1. 1.中国中医科学院西苑医院,中国中医科学院老年病研究所,北京 100091;
    2.北京市中医管理局,北京 100053
  • 收稿日期:2020-04-28 出版日期:2020-12-25 发布日期:2020-12-30
  • 作者简介:孙成成(1989-), 女, 在读博士, 主要从事老年病的中西医结合临床研究和基础研究。E-mail: suncc188@163.com
  • 基金资助:
    北京市科学技术委员会G20工程创新研究“十病十药”研发课题(Z171100001717016)

Neurological Dysfunction and Pathological Changes of Rats with

SUN Chengcheng1, LIU Jiangang1#, LIU Meixia1#, LI Hao1, LUO Zenggang2   

  1. 1. Xiyuan Hospital/Institute of Geriatrics, China Academy of Chinese Medicine Sciences,Beijing 100091, China;
    2. Beijing Municipal Administration of Traditional Chinese Medicine, Beijing 100053, China
  • Received:2020-04-28 Online:2020-12-25 Published:2020-12-30

摘要: 目的 比较大鼠双侧颈总动脉结扎后不同时程的神经功能障碍、脑组织大体病理/显微病理和血清学炎性指标的变化。方法 将SPF级Wistar大鼠麻醉后,施行永久性双侧颈总动脉结扎术。造模成功的大鼠按随机数字表分为术后2周、4周和6周共3组,每组10只。同时设立假手术组,大鼠10只,操作方法同模型组,但只穿线不结扎。分别于术后2周、4周和6周对大鼠进行神经功能检测,然后腹主动脉取血,采用ELISA法检测血清白细胞介素6(interleukin-6,IL-6)、白细胞介素1?(interleukin-1?,IL-1?)和肿瘤坏死因子〈(tumor necrosis factor-〈,TNF-〈)含量。采用脑组织TTC染色法评价脑缺血范围,HE染色后进行显微镜下脑组织形态学观察。结果 与假手术组比较,双侧颈总动脉结扎后2周组、4周组和6周组大鼠的神经功能评分明显降低(P<0.05);与2周组比较,4周组和6周组大鼠的神经功能评分下降明显(P<0.05)。血清炎性指标检测发现,与假手术组比较,不同时程模型组大鼠的IL-6水平明显升高(P<0.05),其余两个指标的差异无统计学意义(P>0.05)。大鼠脑组织病理学观察显示,与假手术组比较,双侧颈总动脉结扎后2周组、4周组和6周组大鼠的脑组织缺血范围随时程延长而增加,脑组织形态也都有不同程度的损伤和炎性浸润。结论 大鼠双侧颈总动脉结扎后脑组织病理改变由缺血发展到梗死灶出现,并伴随神经功能障碍,随时程的延长而变化不同,应根据药物作用机制选择干预时机。

关键词: 双侧颈总动脉结扎, 神经功能障碍, 慢性脑缺血, 炎性因子, 病理改变, 大鼠

Abstract: Objective To compare the changes of neurological dysfunction, gross/microscopic pathology and serum inflammatory index of brain tissues after bilateral common carotid artery ligation in different durations. Methods Permanent bilateral common carotid artery ligation was performed in SPF Wistar rats after anesthesia. The successful modeling rats were randomly divided into 3 groups with 10 in each group; while 10 rats in the sham-operated group were treated by only puncture without ligation. The neurological function of each group was tested 2 weeks, 4 weeks, and 6 weeks postoperatively, and then the blood was taken from the abdominal aorta of the anesthetized rats. ELISA method was used to detect the serum levels of interleukin-6 (IL-6), interleukin-1? (IL-1?) and tumor necrosis factor-? (TNF-?). The brain tissue was stained with triphenyltetrazolium chloride (TTC) to evaluate the range of cerebral ischemia. HE staining was used for morphological observation of the brain tissues. Results Compared with the sham-operated group, the neurological function scores of the rats at 2 weeks, 4 weeks, and 6 weeks after bilateral common carotid artery ligation were decreased significantly (P<0.05). Compared with the 2 weeks group, the neurological function scores of the 4 weeks and 6 weeks groups were decreased significantly (P<0.05). Compared with the sham-operated group, the level of IL-6 in the 2 weeks and 4 weeks groups was significantly increased (P<0.05). Compared with the sham-operated group, the ischemic range of brain tissues increased in the 2 weeks, 4 weeks, and 6 weeks groups. Pathological morphology also showed that the brain tissue morphology of rats in the 2 weeks, 4 weeks and 6 weeks groups had different degrees of damage and inflammatory infiltration. Conclusion After ligation of bilateral common arteries, the pathological changes of the brain tissues vary from ischemia to infarction, accompanied with neurobehavioral dysfunction, and the changes are different over time. Thus, the intervention time should be decided according to the mechanism of drug action.

Key words: Bilateral common carotid artery ligation, Nerve dysfunction, Chronic cerebral ischemia, Inflammatory factors, Pathological changes, Rats

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