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.
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.
Study on protective effects of twin drugs of tetramethylpyrazine-scutellarein on cerebral ischemia-reperfusion injury model rats and its mechanism
To study the protective effects of twin drugs of tetramethylpyrazine-scutellarein (TMSC4) on cerebral ischemia-reperfusion injury (CIRI) model rats and its mechanism.
METHODS
2
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
2
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 (
P
<0.05); the levels of SOD, GSH-Px and CAT and the protein expression of Bcl-2 in brain tissues were significantly decreased (
P
<0.05). Compared with model group, the above indexes of rats were reversed significantly in administration groups (
P
<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 (
P
<0.05).
CONCLUSIONS
2
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
Keywords
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 .
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 .
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 .
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 .