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·药学研究·


          血必净注射液对心脏骤停/心肺复苏后大鼠神经功能及生存情况
          的影响机制
                           Δ


                                                                             2 #
          黄德庆    1, 2* ,高玉广 ,张元侃 ,王政林 ,邓海霞 ,黄夏冰 ,庞 延 ,吴 林 (1.广西中医药大学第一附属医院
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          急诊科,南宁 530023;2.广西中医药大学科学实验中心,南宁 530200)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2024)06-0653-06
          DOI  10.6039/j.issn.1001-0408.2024.06.03
          摘  要  目的  基于 S-亚硝基谷胱甘肽还原酶(GSNOR)/S-亚硝基谷胱甘肽(GSNO)途径探讨血必净注射液对大鼠心脏骤停
         (CA)/心肺复苏(CPR)后神经功能及生存情况影响的潜在机制。方法  以室颤法建立CA/CPR大鼠模型,以假手术组大鼠为参照,
          采用高通量测序分析挖掘两者差异表达基因,并结合酶联免疫吸附测定(ELISA)法检测其海马组织中GSNOR、GSNO含量;筛选
          血必净注射液活性成分,并与GSNOR进行分子对接。将同法造模成功的大鼠分为模型组(30只)、抑制剂(GSNOR抑制剂)组(30
          只)、血必净组(30只)、血必净+抑制剂组(30只),并设置假手术组(30只),分别于药物首次干预后3 h、24 h、3 d时进行神经功能评
          价及生存情况记录,并检测上述时间点各组大鼠海马组织中GSNOR、GSNO含量,分析GSNOR、GSNO含量与大鼠改良的神经系
          统损害严重程度评分表(mNSS)评分的相关性。结果  GSNOR编码基因是模型组与假手术组间的差异表达基因之一;与假手术
          组比较,模型组大鼠海马组织中GSNOR含量显著升高,而GSNO含量显著降低(P<0.05)。血必净注射液中去甲丹参酮、鼠尾草
          酚酮等活性成分与 GSNOR 蛋白的结合能均低于-6 kcal/mol,以氢键连接为主。动物实验结果显示,模型组大鼠各时间点的
          mNSS评分和海马组织中GSNOR含量均显著高于假手术组(P<0.05),生存率和GSNO含量均显著低于假手术组(P<0.05);各给
          药组大鼠上述指标均显著改善,且血必净组mNSS评分显著低于抑制剂组,抑制剂组GSNOR、GSNO含量的变化较血必净组更明
          显,血必净+抑制剂组各指标均显著优于血必净组和抑制剂组(P<0.05)。GSNOR 含量与 mNSS 评分呈正相关,GSNO 含量与
          mNSS 评分呈负相关(P<0.05)。结论  血必净注射液可以改善 CA/CPR 后大鼠的神经功能,提高其生存率,该作用可能与下调
          GSNOR并上调GSNO有关。
          关键词  血必净注射液;心脏骤停;心肺复苏;S-亚硝基谷胱甘肽;S-亚硝基谷胱甘肽还原酶

          Mechanism  of  the  effect  of  Xuebijing  injection  on  neurological  function  and  survival  of  rats  after  cardiac
          arrest/cardiopulmonary resuscitation
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          HUANG Deqing ,GAO Yuguang ,ZHANG Yuankan ,WANG Zhenglin ,DENG Haixia ,HUANG Xiabing ,
                        1, 2
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          PANG Yan ,WU Lin(1.  Dept.  of  Emergency,  the  First  Affiliated  Hospital  of  Guangxi  University  of  Chinese
                   1
                             2
          Medicine,  Nanning  530023,  China;2.  Scientific  Laboratory  Centre,  Guangxi  University  of  Chinese  Medicine,
          Nanning 530200, China)
          ABSTRACT   OBJECTIVE  To  explore  the  potential  mechanism  of  the  effect  of  Xuebijing  injection (XBJ)  on  neurological
          function  and  survival  of  rats  after  cardiac  arrest (CA)/cardiopulmonary  resuscitation (CPR)  based  on  the  S-nitrosoglutathione
          reductase (GSNOR)/S-nitrosoglutathione (GSNO)  pathway.  METHODS  The  CA/CPR  rat  model  was  established  by  ventricular
          fibrillation.  Using  a  sham  operation  group  as  control,  high-throughput  sequencing  was  employed  to  analyze  and  mine  the
          differentially  expressed  genes (DEGs).  Enzyme-linked  immunosorbent  assay  was  used  to  determine  the  contents  of  GSNOR  and
          GSNO  in  the  hippocampus;  the  active  components  of  XBJ  were  screened  and  subjected  to  molecular  docking  analysis  with
          GSNOR.  The  rats  successfully  modeled  using  the  same  method  were  divided  into  model  group (n=30),  inhibitor (GSNOR
          inhibitor)  group (n=30),  XBJ  group (n=30)  and  XBJ+inhibitor  group (n=30),  and  a  sham  operation  group (n=30)  was  set
                                                             up.  Neurological  function  was  evaluated  and  survival  status
             Δ 基金项目 国家自然科学基金地区科学基金项目(No.818607-              was  recorded  at  3  hours,  24  hours  and  3  days  after  the  first
          89);广西高校中青年教师科研基础能力提升项目(No.2021KY0281);            drug  intervention.  The  contents  of  GSNOR  and  GSNO  in  the
          广西壮族自治区中医药管理局自筹经费科研课题(No.GXZYZ2021-
                                                             hippocampus  of  rats  were  determined  in  each  group  at  the
          0191)                                              above  time  points,  and  the  relationship  of  the  contents  of
             *第一作者 副主任医师,硕士。研究方向:中医药防治脑系疾
                                                             GSNOR  and  GSNO  with  modified  neurologic  severity  scale
          病、急危重症。E-mail:huangdq@gxtcmu.edu.cn
             # 通信作者 主任医师,博士。研究方向:中医药防治脑系疾病、神                (mNSS)  score  was  analyzed.  RESULTS  GSNOR  coding  gene
          经重症。E-mail:15177775008@139.com                     was  differentially  expressed  between  the  model  group  and  the


          中国药房  2024年第35卷第6期                                                 China Pharmacy  2024 Vol. 35  No. 6    · 653 ·
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