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...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 Orai,suggesting that it has a protective effect against subacute CIRI.展开更多
本文旨在报道1例猫鼻神经内分泌恶性肿瘤的病理和免疫组化特征。4岁雄性英国短毛猫,在他院按肺炎治疗一个月未见好转遂转至本院,检查发现鼻部肿块,手术活检取鼻腔肿块进行组织病理学和免疫组化检查。组织病理学结果显示肿瘤细胞大小形...本文旨在报道1例猫鼻神经内分泌恶性肿瘤的病理和免疫组化特征。4岁雄性英国短毛猫,在他院按肺炎治疗一个月未见好转遂转至本院,检查发现鼻部肿块,手术活检取鼻腔肿块进行组织病理学和免疫组化检查。组织病理学结果显示肿瘤细胞大小形态不一,异型性明显,细胞核多呈泡状,且已侵袭至周围组织;免疫组化结果显示神经元特异性烯醇化酶(neuron specific enolase,NSE)、突触素(synaptophysin,Syn)、血管活性肠肽(vasoactive intestinal peptide,VIP)、CD99(cluster of differentiation 99,CD99)呈阳性。根据实验室检查、组织病理学以及免疫组化结果,最后诊断为鼻神经内分泌恶性肿瘤,更倾向于低分化神经内分泌癌(neuroendocrine carcinoma,NEC)。本病例可为诊断该肿瘤并与其他鼻腔肿瘤相区分提供参考依据。展开更多
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)。
文摘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 Orai,suggesting that it has a protective effect against subacute CIRI.
文摘本文旨在报道1例猫鼻神经内分泌恶性肿瘤的病理和免疫组化特征。4岁雄性英国短毛猫,在他院按肺炎治疗一个月未见好转遂转至本院,检查发现鼻部肿块,手术活检取鼻腔肿块进行组织病理学和免疫组化检查。组织病理学结果显示肿瘤细胞大小形态不一,异型性明显,细胞核多呈泡状,且已侵袭至周围组织;免疫组化结果显示神经元特异性烯醇化酶(neuron specific enolase,NSE)、突触素(synaptophysin,Syn)、血管活性肠肽(vasoactive intestinal peptide,VIP)、CD99(cluster of differentiation 99,CD99)呈阳性。根据实验室检查、组织病理学以及免疫组化结果,最后诊断为鼻神经内分泌恶性肿瘤,更倾向于低分化神经内分泌癌(neuroendocrine carcinoma,NEC)。本病例可为诊断该肿瘤并与其他鼻腔肿瘤相区分提供参考依据。
