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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
1
1
1
1
1
1
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
1
1
1
HUANG Deqing ,GAO Yuguang ,ZHANG Yuankan ,WANG Zhenglin ,DENG Haixia ,HUANG Xiabing ,
1, 2
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1
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 ·