Effects of total flavonoids of Rhododendra simsii on ameliorating brain injury via G protein-coupled SOCE pathway mediated by STIM and Orai in subacute phase of ischemia/reperfusion  

作　　者：LU Jia-jun JIANG Chen-chen HE Yu-xiang SHI Lei YIN Xiu-yun CHEN Zhuo CAO Di HAN Jun 

机构地区：[1]Department of Pharmacology,Drug Research and Development Center,School of pharmacy,Wannan Medical College,Wuhu 241002,China [2]Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui,Wuhu 241002,China [3]Anhui Provincial Engineering Research Center for Polysaccharide Drugs,Wuhu 241002,China

出　　处：《中国药理学与毒理学杂志》2021年第10期768-769,共2页Chinese Journal of Pharmacology and Toxicology

基　　金：National Natural Science Foundation of China(81173596);and Major Project of Natural Science Foundation of the Department of Education of Anhui Province(KJ2019ZD32)。

摘　　要：OBJECTIVE To explore the effect of total flavonoids of Rhododendra simsii(TFR)on improving cerebral ischemia/reperfusion injury(CIRI)and its relationship with STIM/Orai-regulated operational Ca^(2+)influx(SOCE)pathway.METHODS Oxygen-glucose deprivation/reoxygenation(OGD/R)PC12 cells were used to simulate CIRI in vitro,and the intracellular Ca^(2+)concentration and apoptosis rate of PC12 cells were detected by laser confocal microscope and flow cytometry,respectively.The regulation of STIM/Orai on SOCE was analyzed by STIM/Orai gene silencing and STIM/O rai gene overexpression.The CIRI model was established by MCAO in SD rats.The activities of inflammatory cytokines IL^(-1),IL-6 and TNF-αin serum were detected by ELISA.The pathological changes of ischemic brain tissue and the infarction of rat brain tissue were detected by HE staining and TTC staining.The protein and mRNA expression levels of STIM1,STIM2,Orai1,caspase-3 and PKB in brain tissue were detected by Western blotting and RT-qPCR,respectively.RESULTS The results of in vitro experiment showed that the fluorescence intensity of Ca^(2+)and apoptosis rate in PC12 cells treated with TFR were significantly lower than those in OGD/R group,and this trend was enhanced by SOCE antagonist 2-APB.STIM1/STIM2/Orai1 gene silencing significantly reduced apoptosis and Ca^(2+)overload in OGD/R model,while TFR combined with overexpression of STIM1/STIM2/Orai1 aggravated apoptosis and Ca2+overload.In the in vivo experiment,TFR significantly reduced the brain histopathological damage,infarction of brain tissue,the contents of IL^(-1),IL-6 and TNF-αin the serum in MCAO rats and down-regulated the expression of STIM1,STIM2,Orai1 and caspase-3 protein and mRNA in the brain tissue,and up-regulated the expression of PKB.The above effects were enhanced by the addition of 2-APB.CONCLUSION The above results indicate that TFR may reduce the contents of inflammatory factors and apoptosis,decrease Ca2+overload and ameliorate brain injury by inhibiting SOCE pathway mediated by STIM and

关 键 词：total flavonoids of Rhododendra simsii cerebral ischemia/reperfusion injury STIM/Orai store-operated calcium entry 2-APB 

分 类 号：R285[医药卫生—中药学]