Page 75 - 《中国药房》2023年13期
P. 75

中风瘀热方对缺血性脑卒中模型大鼠的干预作用及机制
                                                                                                Δ


                                                     1, 2 #
                                    2
                            3
          李 琬    1, 2* ,刘炳周 ,鞠建明 ,彭蕴茹 ,王 云 (1. 南京中医药大学附属中西医结合医院药剂科,南京
                                             2
          210028;2.江苏省中医药研究院,南京 210028;3.山东省寿光市人民医院药剂科,山东 寿光 262700)
          中图分类号  R285.5;R965      文献标志码  A      文章编号  1001-0408(2023)13-1601-05
          DOI  10.6039/j.issn.1001-0408.2023.13.11

          摘  要  目的 研究中风瘀热方对缺血性脑卒中模型大鼠的干预作用及机制。方法  将85只大鼠随机分为假手术组(生理盐水,
          n=15)、模型对照组(生理盐水,n=18)、尼莫地平片组(阳性对照,10.8 mg/kg,n=18)和中风瘀热方高剂量组(20.52 g/kg,n=17)、
          中风瘀热方低剂量组(5.13 g/kg,n=17)。预防性连续给药7 d(每天1次)后,除假手术组外,其余各组均采用改良线栓法制备大鼠
          大脑中动脉阻塞(MCAO)模型。造模成功后,各组大鼠继续给药3 d。实验期间,观察大鼠一般情况,进行神经功能评分;末次给
          药后,计算脏器指数,观察大鼠脑梗死面积及脑组织病理形态学变化,检测大鼠脑组织及血清中肿瘤坏死因子α(TNF-α)、白细胞
          介素6(IL-6)水平及脑组织中胱天蛋白酶3(caspase-3)、磷酸化蛋白激酶B(p-AKT)蛋白的平均光密度值。结果  造模3 d后,与假
          手术组比较,模型对照组大鼠神经功能评分,脑指数、脾指数,脑梗死面积占比,脑组织和血清中TNF-α、IL-6水平,脑组织中cas‐
          pase-3蛋白平均光密度值均显著升高(P<0.05或P<0.01);脑组织出现核固缩、弥散性水肿等病变。与模型对照组比较,各给药
          组上述指标均有不同程度的改善,其中中风瘀热方高剂量组大鼠脑指数、脾指数,脑梗死面积占比,脑组织和血清中TNF-α水平,
          脑组织中caspase-3蛋白和p-AKT蛋白的平均光密度值均显著回调(P<0.05或P<0.01)。结论  中风瘀热方对MCAO模型大鼠有
          一定的防治作用;其机制可能是通过减少炎症因子TNF-α、IL-6的分泌,下调缺血侧脑组织中caspase-3蛋白表达,上调缺血侧脑组
          织中p-AKT蛋白表达,从而达到保护神经元的作用。
          关键词  中风瘀热方;缺血性脑卒中;大脑中动脉阻塞模型;胱天蛋白酶3;磷酸化蛋白激酶B;大鼠

          Intervention effect and mechanism of Zhongfeng yure decoction on ischemic stroke model rats
                                              2
                                                           2
          LI Wan ,LIU Bingzhou ,JU Jianming ,PENG Yunru ,WANG Yun (1.  Dept.  of  Pharmacy,  the  Affiliated
                1, 2
                                3
                                                                        1,2
          Hospital  of  Integrated  Traditional  Chinese  and  Western  Medicine  of  Nanjing  University  of  Chinese  Medicine,
          Nanjing 210028, China;2. Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China;
          3.  Dept.  of  Pharmacy,  Shouguang  Municipal  People’s  Hospital  of  Shandong  Province,  Shandong  Shouguang
          262700, China)
          ABSTRACT   OBJECTIVE  To  study  the  intervention  effect  and  mechanism  of  Zhongfeng  yure  decoction  on  ischemic  stroke
          model  rats.  METHODS  Totally  85  rats  were  randomly  divided  into  sham  operation  group (normal  saline,  n=15),  model  control
          group (normal  saline,  n=18),  Nimodipine  tablet  group (positive  control,  10.8  mg/kg,  n=18),  high-dose  group  of  Zhongfeng
          yure  decoction (20.52  g/kg,  n=17)  and  low-dose  group  of  Zhongfeng  yure  decoction (5.13  g/kg,  n=17),  respectively. After  7
          days  of  preventive  continuous  administration (once  a  day),  except  for  the  sham  operation  group,  the  rats’  middle  cerebral  artery
          occlusion (MCAO)  model  was  established  by  the  modified  suture  method  in  other  groups. After  modeling,  the  rats  in  each  group
          continued  to  be  administered  for  3  days.  During  experiment,  general  condition  of  the  rats  was  observed,  and  the  neurological
          function  score  was  performed.  After  the  last  administration,  the  organ  index  was  calculated,  the  cerebral  infarction  area  and
          pathological changes of brain tissue were observed. The levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in brain
          tissue and serum, and the average optical density value of caspase-3 and phosphorylated protein kinase B(p-AKT) protein in brain
          tissue were detected. RESULTS Three days after modeling, compared with sham operation group, the neurological function score,
          in brain tissue index, spleen tissue index, proportion of cerebral infarction area, the levels of TNF-α and IL-6 in brain tissue and
          serum,  and  the  average  optical  density  value  of  caspase-3  protein  in  brain  tissue  were  significantly  increased  in  the  model  control
          group (P<0.05  or  P<0.01);  karyopyknosis,  diffuse  edema  and  other  lesions  appeared  in  brain  tissue.  Compared  with  the  model
                                                             control  group,  the  above  indexes  in  each  administration  group
             Δ 基金项目 江苏省中西医结合医院院内制剂资助项目(No.                   were  improved  to  varying  degrees.  Among  them,  there  were
          YNZJ1920)                                          significant  regression  in  brain  tissue  index,  spleen  tissue
             *第一作者 主管中药师。研究方向:中药新产品研发及药效物质
                                                             index,  proportion  of  cerebral  infarction  area,  TNF-α  level  in
          基础。E-mail:303692783@qq.com
             # 通信作者 主管中药师,硕士。研究方向:中药新剂型、新工艺及                 brain  tissue  and  serum,  and  the  average  optical  density  values
          中药质量控制。E-mail:632307956@qq.com                     of  caspase-3  protein  and  p-AKT  protein  in  brain  tissue  of  rats


          中国药房  2023年第34卷第13期                                              China Pharmacy  2023 Vol. 34  No. 13    · 1601 ·
   70   71   72   73   74   75   76   77   78   79   80