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平肝活血散对大鼠脑缺血再灌注损伤的影响及作用机制初探
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宋发萍 ,张 洁 ,唐 勇 ,刘宗梅 ,王晓玲 (1.陕西中医药大学第一临床医学院,陕西 咸阳 712000;2.安
康市中医医院脑病科,陕西 安康 725000)
中图分类号 R932;R285 文献标志码 A 文章编号 1001-0408(2022)24-2999-06
DOI 10.6039/j.issn.1001-0408.2022.24.11
摘 要 目的 探讨平肝活血散对大鼠脑缺血再灌注损伤(CIRI)的影响及作用机制。方法 采用线栓法制备CIRI模型。将大鼠
分为假手术组、模型组、阳性对照组(通心络胶囊0.325 g/kg)和平肝活血散低、中、高剂量组(3.02、6.04、12.08 g/kg),每组12只。各
组大鼠灌胃等量水或对应药液,每日1次,连续14 d。干预第1、7、14天对大鼠神经功能进行Longa评分。末次给药后,测定大鼠
脑梗死体积百分比,观察神经元损伤(神经元密度)和凋亡情况,检测脑缺血皮层中p53、B淋巴细胞瘤2(Bcl-2)、Bcl-2相关X蛋白
(Bax)、胱天蛋白酶3(Caspase-3)、活化Caspase-3(Cleaved Caspase-3)蛋白表达水平。结果 与假手术组比较,模型组大鼠干预第
1、7、14天的Longa评分、脑梗死体积百分比均显著升高(P<0.05);脑缺血皮层细胞排列紊乱,尼氏小体缺失、空泡,出现大量细胞
凋亡;病灶侧神经元密度、Bcl-2蛋白表达均显著降低(P<0.05),脑缺血皮层中p53、Bax、Caspase-3、Cleaved Caspase-3蛋白表达均
显著升高(P<0.05或P<0.01)。与模型组比较,平肝活血散高剂量组大鼠脑缺血皮层中Bcl-2表达均显著升高(P<0.05);平肝活
血散中、高剂量组大鼠干预第7、14天的Longa评分均显著降低(P<0.05),其余指标亦显著逆转(P<0.05或P<0.01)。结论 平肝
活血散可保护CIRI模型大鼠脑神经,抑制细胞凋亡;其机制可能与下调p53、Bax、Caspase-3蛋白表达,上调Bcl-2蛋白表达有关。
关键词 平肝活血散;脑缺血再灌注损伤;细胞凋亡;大鼠
Preliminary study on the effect of Pinggan huoxue powder on cerebral ischemia-reperfusion injury in rats
and its mechanism
SONG Faping ,ZHANG Jie ,TANG Yong ,LIU Zongmei ,WANG Xiaoling(1. The First Clinical College,
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Shaanxi University of Chinese Medicine, Shaanxi Xianyang 712000, China;2. Dept. of Neurology,Ankang
Hospital of Traditional Chinese Medicine,Shaanxi Ankang 725000, China)
ABSTRACT OBJECTIVE To investigate the effect and mechanism of Pinggan huoxue powder on cerebral ischemia-reperfusion
injury (CIRI) in rats. METHODS CIRI model was induced by suture-occluded method. SD rats were divided into sham operation
group, model group, positive control group (Tongxinluo capsule 0.325 g/kg), Pinggan huoxue powder low-dose, medium-dose
and high-dose groups (3.02, 6.04, 12.08 g/kg), with 12 rats in each group. Each group was given constant volume of water or
drug intragastrically, once a day, for consecutive 14 d. Longa score was used to evaluate neurological function of rats on the 1st,
7th and 14th day of intervention. After the last administration, the percentage of cerebral infarction volume in rats was measured,
and neuronal injury (neuronal density) and neuronal apoptosis were observed; the protein expressions of p53, B cell lymphoma-2
(Bcl-2), Bcl-2 associated X protein (Bax), Caspase-3 and activated Caspase-3 (Cleaved caspase-3) in brain tissue were detected.
RESULTS Compared with sham operation group, Longa score at the 1st, 7th and 14th day of intervention and the percentage of
cerebral infarction volume in model group significantly increased (P<0.05), and the arrangement of cortical cells in ischemic side
was disordered, Nissl bodies were absent and vacuolated, and a large number of cell apoptosis occurred. The neuronal density and
protein expression of Bcl-2 at the lesion side were significantly decreased (P<0.05), while the protein expressions of p53, Bax,
Caspase-3 and Cleaved Caspase-3 were significantly increased (P<0.05 or P<0.01). Compared with model group, the expressions
of Bcl-2 in cerebral ischemia cortex of rats in Pinggan huoxue powder high-dose group were significantly increased (P<0.05).
Longa scores of rats in Pinggan huoxue powder medium-dose and high-dose groups on the 7th and 14th day of intervention were
significantly decreased (P<0.05), and other indexes were also significantly reversed (P<0.05 or P<0.01). CONCLUSIONS
Pinggan huoxue powder can protect cerebral nerves and inhibit
Δ 基金项目 陕西省中医药管理局课题(No.2021-GJ-JC011);陕西
apoptosis of CIRI model rats, the mechanism of which may be
省 2021 年度中医药传承创新暨“秦药”开发重点科学研究项目(No.
related to down-regulating the protein expressions of p53, Bax
2021-01-GJ-019)
and Caspase-3 and up-regulating the protein expression of
*第一作者 主治医师。研究方向:脑血管病的基础与临床治疗。
电话:029-87080532。E-mail:710043936@qq.com Bcl-2.
# 通信作者 主任医师。研究方向:脑血管病的基础与临床治疗。 KEYWORDS Pinggan huoxue powder; cerebral ischemia-
电话:0915-8183605。E-mail:akwxl@163.com reperfusion injury; apoptosis; rat
中国药房 2022年第33卷第24期 China Pharmacy 2022 Vol. 33 No. 24 · 2999 ·