Study on protective effects of twin drugs of tetramethylpyrazine-scutellarein on cerebral ischemia-reperfusion injury model rats and its mechanism

CHEN Lina; WEN Jinlan; ZHANG Shanhui; LU Jun; ZHAO Fuhui; LONG Tiemei; DONG Li; DONG Yongxi

doi:10.6039/j.issn.1001-0408.2023.15.03

您当前的位置：

首页 >

文章列表页 >

Study on protective effects of twin drugs of tetramethylpyrazine-scutellarein on cerebral ischemia-reperfusion injury model rats and its mechanism

更新时间：2023-08-10

- Study on protective effects of twin drugs of tetramethylpyrazine-scutellarein on cerebral ischemia-reperfusion injury model rats and its mechanism
- ZHONGGUO YAOFANG Vol. 34, Issue 15, Pages: 1804-1808(2023)
- 作者机构：
  
  贵州医科大学药学院，贵阳　550025
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.15.03
  CLC： R965
- Published：15 August 2023，
  
  Received：07 February 2023，
  
  Revised：17 June 2023，
扫描看全文
陈莉娜,文金兰,张善惠等.川芎嗪-灯盏乙素苷元孪药对脑缺血再灌注损伤模型大鼠的保护作用及机制研究 ^Δ[J].中国药房,2023,34(15):1804-1808.

CHEN Lina,WEN Jinlan,ZHANG Shanhui,et al.Study on protective effects of twin drugs of tetramethylpyrazine-scutellarein on cerebral ischemia-reperfusion injury model rats and its mechanism[J].ZHONGGUO YAOFANG,2023,34(15):1804-1808.
陈莉娜,文金兰,张善惠等.川芎嗪-灯盏乙素苷元孪药对脑缺血再灌注损伤模型大鼠的保护作用及机制研究 ^Δ[J].中国药房,2023,34(15):1804-1808. DOI： 10.6039/j.issn.1001-0408.2023.15.03.

CHEN Lina,WEN Jinlan,ZHANG Shanhui,et al.Study on protective effects of twin drugs of tetramethylpyrazine-scutellarein on cerebral ischemia-reperfusion injury model rats and its mechanism[J].ZHONGGUO YAOFANG,2023,34(15):1804-1808. DOI： 10.6039/j.issn.1001-0408.2023.15.03.

摘要

目的

研究川芎嗪-灯盏乙素苷元孪药（TMSC4）对脑缺血再灌注损伤（CIRI）模型大鼠的保护作用及机制。

方法

将105只SD大鼠随机分为假手术组、模型组、灯盏乙素苷元组（0.7 mmol/kg）、川芎嗪组（0.7 mmol/kg）和TMSC4低、中、高剂量组（0.35、0.7、1.4 mmol/kg），每组15只。假手术组、模型组大鼠灌胃等体积生理盐水，其余各组大鼠灌胃相应药物，每天1次，连续 14 d。除假手术组外，其余各组大鼠均采用线栓法建立CIRI模型。大鼠缺血2 h再灌注22 h后，测定大鼠脑指数及脑含水量；检测大鼠血清中白细胞介素1β（IL-1β）、IL-6、肿瘤坏死因子α

（

TNF

）

的水平，脑组织中超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化氢酶（GSH-Px）、过氧化氢酶（CAT）的水平和大脑皮层神经细胞的凋亡情况以及B细胞淋巴瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）、活化型胱天蛋白酶3（cleaved-caspase-3）蛋白表达水平。

结果

与假手术组比较，模型组大鼠脑指数和脑含水量，血清中IL-1β、IL-6、TNF-α水平以及脑组织中MDA水平，神经细胞凋亡率，Bax、cleaved-caspase-3蛋白表达水平均显著升高（

＜0.05）；脑组织中SOD、 GSH-Px、CAT水平和Bcl-2蛋白表达水平均显著降低（

＜0.05）。与模型组比较，各给药组大鼠上述指标水平均显著逆转（

＜0.05），且TMSC4中、高剂量组的逆转作用显著优于灯盏乙素苷元组和川芎嗪组（

＜0.05）。

结论

TMSC4对CIRI模型大鼠具有保护作用，其作用机制可能与减轻炎症反应、氧化应激损伤，抑制神经细胞凋亡有关。

Abstract

OBJECTIVE

To study the protective effects of twin drugs of tetramethylpyrazine-scutellarein （TMSC4） on cerebral ischemia-reperfusion injury （CIRI） model rats and its mechanism.

METHODS

One hundred and five SD rats were randomly divided into sham operation group， model group， scutellarein group （0.7 mmol/kg）， tetramethylpyrazine group （0.7 mmol/kg）， and TMSC4 low-dose， medium-dose and high-dose groups （0.35， 0.7， 1.4 mmol/kg）， with 15 rats in each group. Sham operation group and model group were given constant volume of normal saline intragastrically， and other groups were given relevant drug intragastrically， once a day， for consecutive 14 d. Except for sham operation group， all other groups were treated to establish the CIRI model using the thread occlusion method. After 2 hours of ischemia and 22 hours of reperfusion， the brain index and brain water content of the rats were measured. Serum levels of interleukin 1β （IL-1β）， IL-6 and tumor necrosis factor α （TNF-α）， the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px） and catalase （CAT） in brain tissues， the situation of neuronal cell apoptosis， and the protein expressions of B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax） and cleaved-caspase-3 were evaluated.

RESULTS

Compared with sham operation group， the brain index， brain water content， the serum levels of IL-1β， IL-6 and TNF-α

，

the levels of MDA in brain tissues， the brain cell apoptosis and the protein expressions of Bax and cleaved-caspase-3 in model group were significantly increased （

＜0.05）； the levels of SOD， GSH-Px and CAT and the protein expression of Bcl-2 in brain tissues were significantly decreased （

＜0.05）. Compared with model group， the above indexes of rats were reversed significantly in administration groups （

＜0.05）， while the reverse effects of TMSC4 medium-dose and high-dose groups were significantly better than those of scutellarein group and tetramethylpyrazine group （

＜0.05）.

CONCLUSIONS

TMSC4 has a certain protective effect in CIRI model rats， the mechanism of which may be related to relieving inflammatory reaction and oxidative stress， inhibiting cell apoptosis.

关键词

川芎嗪灯盏乙素苷元孪药脑缺血再灌注损伤神经保护大鼠

Keywords

scutellareintwin drugscerebral ischemia-reperfusion injuryneuroprotective effectrat

references

ZHOU M G，WANG H D，ZENG X Y，et al. Mortality，morbidity，and risk factors in China and its provinces，1990-2017：a systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet，2019，394（10204）：1145-1158.

OZONER B，YUCELI S，AYDIN S，et al. Effects of pycnogenol on ischemia/reperfusion-induced inflammatory and oxidative brain injury in rats[J]. Neurosci Lett，2019，704：169-175.

GUO L，HUANG Z X，HUANG L J，et al. Surface-modified engineered exosomes attenuated cerebral ische- mia/reperfusion injury by targeting the delivery of quercetin towards impaired neurons[J]. J Nanobiotechnology，2021，19（1）：141.

QIAN W D，XIONG X J，FANG Z Y，et al. Protective effect of tetramethylpyrazine on myocardial ischemia-reperfusion injury[J]. Evid Based Complement Alternat Med，2014，2014：107501.

LI G L，LI G L，TIAN Y F，et al. A novel ligustrazine derivative T-VA prevents neurotoxicity in differentiated PC12 cells and protects the brain against ischemia injury in CIRI rats[J]. Int J Mol Sci，2015，16（9）：21759-21774.

WU D R，CHEN J，LUO K K，et al. Design，synthesis and evaluation of novel scutellarin and scutellarein-N，N-bis-substituted carbamate-l-amino acid derivatives as potential multifunctional therapeutics for Alzheimer’s disease[J]. Bioorg Chem，2022，122：105760.

WU S X，LIU M J，WEN J L，et al. Hybrid molecules of scutellarein and 3，5，6-trimethylpyrazine-2-formic acid linked with polar amino acid for ischemic stroke[J]. Med Chem Res，2022，31（6）：916-924.

刘明吉，吴淑霞，雷丹丹，等. 川芎嗪灯盏乙素苷元抗缺血性脑卒中孪药的合成及活性研究[J]. 中国新药杂志，2021，30（3）：267-273.

DONG Y X，DONG L，CHEN J L，et al. Synthesis and biological evaluation of N-alkyl-1，4-dihydroquinoline prodrugs of scutellarin methyl ester as neuroprotective agents[J]. Med Chem Res，2018，27（4）：1111-1121.

徐芳琴，郭超，王婧雯. 山柰酚对脑缺血/再灌注损伤的体内外保护作用机制研究[J]. 中国药房，2022，33（17）：2065-2071.

汪继涛，刘天龙，李玉文. Z-没药甾酮联合11-羰基-β-乙酰乳香酸对脑缺血再灌注损伤模型大鼠的改善作用研究[J]. 中国药房，2019，30（24）：3354-3359.

YIN L H，TANG T，LIN Y J，et al. Functional connectivity of ipsilateral striatum in rats with ischemic stroke increased by electroacupuncture[J]. J Integr Neurosci，2022，21（6）：162.

马贤德，孙宏伟，柴纪严，等.线栓法制备大鼠脑缺血再灌注模型的方法研究[J]. 中华中医药学刊，2009，27（6）：1200-1201.

LIU M，XU Z P，WANG L，et al. Cottonseed oil alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia and astrocyte[J]. J Neuroinflammation，2020，17（1）：270.

CHOUCHANI E T，PELL V R，GAUDE E，et al. Ischae- mic accumulation of succinate controls reperfusion injury through mitochondrial ROS[J]. Nature，2014，515（7527）：431-435.

SAMARGHANDIAN S，AZIMI-NEZHAD M，FARKHONDEH T，et al. Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain，liver and kidney[J]. Biomedecine Pharmacother，2017，87：223-229.

WANG L F，SUN J，YI Q D，et al. Protective effect of polyphenols extract of adlay （Coix lachryma-jobi L. var. ma-yuen Stapf） on hypercholesterolemia-induced oxidative stress in rats[J]. Molecules，2012，17（8）：8886-8897.

LI Z X，XIAO G X，WANG H Y，et al. A preparation of Ginkgo biloba L. leaves extract inhibits the apoptosis of hippocampal neurons in post-stroke mice via regulating the expression of Bax/Bcl-2 and caspase-3[J]. J Ethnopharmacol，2021，280：114481.

YANG L，TAO Y W，LUO L L，et al. Dengzhan Xixin injection derived from a traditional Chinese herb Erigeron breviscapus ameliorates cerebral ischemia/reperfusion injury in rats via modulation of mitophagy and mitochondrial apoptosis[J]. J Ethnopharmacol，2022，288：114988.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Study on metabolites derived from Zhideke granules in rats in vivo

Effects of Yiru tiaojing granules on the pharmacokinetics of olanzapine in rats

Improvement effects of Shangke xiaoyan hydrogel plaster on osteoarthritis model rats

Intervention effect and mechanism of Zhongfeng yure decoction on ischemic stroke model rats

Improvement effect and mechanism of different extracts from Tylophora yunnanensis on non-alcoholic steatohepatitis

Related Author

LIANG Jie

ZHENG Piaoxue

CHEN Huihua

HUANG Chunyan

LIANG Yanli

LU Chunlian

XIE Jingjing

MA Yuming

Related Institution

Dept. of Pharmacy， Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine

Qinzhou Inspection and Testing Center

Guangxi Zhuang Yao Medicine Engineering Technology Research Center

National Engineering Research Center South China Branch of TCM Solid Preparation Manufacturing Technology

Guangxi Universities Laboratory of TCM Extraction， Purification and Quality Analysis

Address：8/F,129 Daping Main Street,Yuzhong District,Chongqing 400042,P.R.China
Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号公网安备50010302001817
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰