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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 ·
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