中国药物警戒 ›› 2024, Vol. 21 ›› Issue (10): 1095-1102.
DOI: 10.19803/j.1672-8629.20240281

• 基础与临床研究 • 上一篇    下一篇

不同时间点使用活血化瘀法对急性期脑出血大鼠血肿体积及神经功能缺损程度的影响

邢毅超1, 刘若凡2, 王悦3, 张根明1,*   

  1. 1北京中医药大学东直门医院脑病科,北京 100700;
    2山东中医药大学附属医院老年医学中心,山东 济南 250014;
    3北京市怀柔区中医医院脑病科,北京 101400
  • 收稿日期:2024-04-30 出版日期:2024-10-15 发布日期:2024-10-14
  • 通讯作者: *张根明,男,博士,教授,中医药防治脑血管病。E-mail:zhanggenming@163.com
  • 作者简介:邢毅超,女,硕士,中医药防治脑病。
  • 基金资助:
    国家重点研发计划(2019YFC171200); 2020年科技创新专项(DZMKJCX-2020-022); 横向课题资助项目(HX-DZM 2018004)

Effect of blood-activating and stasis resolution therapy on hematoma volume and neurological deficit in rats with acute cerebral hemorrhage across different time points

XING Yichao1, LIU Ruofan2, WANG Yue3, ZHANG Genming1,*   

  1. 1Department of Neurology, Beijing University of Chinese Medicine, Dongzhimen Hospital, Beijing 100700, China;
    2Department of Geriatric Medicine, the Affiliated Hospital of Shandong University of Chinese Medicine, Jinan Shandong 250014, China;
    3Department of Neurology, Beijing Huairou Hospital of Traditional Chinese Medicine, Beijing 101400, China
  • Received:2024-04-30 Online:2024-10-15 Published:2024-10-14

摘要: 目的 观察不同时机使用活血化瘀法对急性期脑出血大鼠血肿体积及神经功能缺损程度的影响,探讨脑出血急性期应用活血化瘀法是否有增加血肿大小的风险,比较不同时机用药的作用效果,并探究其作用机制。方法 将40只SPF级SD大鼠随机分为假手术组、模型组和实验组。其中,实验组根据首次给药时间先后分为预给药组、6 h组、24 h组。使用尾状核注射Ⅶ型胶原酶诱导大鼠脑出血。造模前,预给药组于连续7 d予脑血疏口服液每日灌胃给药,其余各组每日予等量生理盐水。造模成功后,预给药组和6 h组于造模后6 h首次给药,24 h组于造模后24 h首次给药,假手术组和模型组予等量生理盐水,至造模后72 h。上述过程中给药或给水均间隔24 h 1次。造模后24 h和72 h用磁共振成像技术对血肿体积进行评估,用改良神经功能缺损评分标准对大鼠行为学进行记录和评估,用Western Blot法测定大鼠脑组织中CD36表达水平。结果 血肿体积评估:与造模后24 h相比,造模后72 h时预给药组、6 h组、24 h组血肿体积显著减小(P<0.05);组间比较显示各实验组造模的血肿清除率均小于模型组(P<0.01)。神经功能缺损评分:造模后72 h,与模型组相比,各实验组神经功能缺损评分显著降低(P<0.05)。CD36表达:造模后72 h,预给药组及6 h组CD36表达较模型组显著升高(P<0.05)。结论 急性期使用活血化瘀法不会增加出血风险,超早期用药血肿清除作用更强,其作用机制可能为介导CD36促进小胶质细胞的吞噬功能,不等同于西药的抗栓或抗凝药。

关键词: 脑出血, 急性期, 脑血疏口服液, 活血化瘀法, 用药时间, 大鼠, 血肿体积, 神经功能

Abstract: Objective To observe the effect of activating blood circulation and resolving stasis at different time points on the volume of hematoma and the degree of neurological deficit in rats with acute intracerebral hemorrhage, explore whether the adoption of this method during the acute phase increases the risk of hematoma expansion, compare the effects of medication at different timing, and to explore its mechanism of action. Methods Forty SPF-grade SD rats were randomly divided into three groups: the sham operation group, model group, experimental group. The experimental group was divided into pre-administration group, 6 h group and 24 h group according to the time of first administration. Intracerebral hemorrhage in rats was induced by injection of type Ⅶ collagenase into the caudate nucleus. Before modeling, the pre-administration group was given Naoxueshu oral liquid daily by intragastric administration for 7 consecutive days, and the other groups were given the same amount of normal saline daily. After the modeling was successful, the pre-administration group and the 6 h group were given the first dose at 6 h after the modeling, the 24 h group was given the first dose at 24 h after the modeling, and the sham operation group and the model group were given the same amount of normal saline until 72 h after the modeling. Magnetic resonance imaging was used to assess hematoma volumes 24 and 72 hours after modeling, and the behavioral neurology of rats was recorded and evaluated using the modified Neurological Deficit Score. Finally, the expression level of CD36 in rat brain tissue was determined using Western blot. Results Evaluation of hematoma volumes: Compared with 24 hours after modeling, the hematoma volumes in the pre-administration group, 6-hour group, and 24-hour group were significantly reduced at 72 hours after modeling (P<0.05). Intergroup comparison showed that the hematoma clearance rate in each experimental group was lower than that of the model group (P<0.01). Neurological deficit score: At 72 hours after modeling, the neurological deficit scores in the experimental groups were significantly lower than those in the model group (P<0.05). CD36 expression: At 72 hours after modeling, the expressions of CD36 in the pre-administration group and 6-hour group were significantly higher than that of the model group (P<0.05). Conclusion The method of activating blood and resolving stasis during the acute phase does not increase the risk of bleeding, and the effect of early medication on hematoma clearance is stronger. The mechanism of action may be related to promotion of the phagocytic function of microglia after mediation by CD36, unlike anticoagulant or antiplatelet drugs.

Key words: cerebral hemorrhage, acute, Naoxueshu oral liquid, activating blood and resolving stasis, timing of medication, rats, hematoma volume, neurological function

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