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银杏二萜内酯葡胺注射液通过下调calpain信号通路抑制脑缺血神经细胞凋亡

刘秋, 许治良, 金治全, 周军, 毕宇安, 王振中, 萧伟

刘秋, 许治良, 金治全, 周军, 毕宇安, 王振中, 萧伟. 银杏二萜内酯葡胺注射液通过下调calpain信号通路抑制脑缺血神经细胞凋亡[J]. 中国药科大学学报, 2015, 46(6): 707-711. DOI: 10.11665/j.issn.1000-5048.20150612
引用本文: 刘秋, 许治良, 金治全, 周军, 毕宇安, 王振中, 萧伟. 银杏二萜内酯葡胺注射液通过下调calpain信号通路抑制脑缺血神经细胞凋亡[J]. 中国药科大学学报, 2015, 46(6): 707-711. DOI: 10.11665/j.issn.1000-5048.20150612
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LIU Qiu, XU Zhiliang, JIN Zhiquan, ZHOU Jun, BI Yu′an, WANG Zhenzhong, XIAO Wei. Diterpene ginkgolides meglumine injection attenuates oxygen-glucose deprivation-induced apoptosis of nerve cells via inhibition of calpain signaling pathway[J]. Journal of China Pharmaceutical University, 2015, 46(6): 707-711. DOI: 10.11665/j.issn.1000-5048.20150612
Citation: LIU Qiu, XU Zhiliang, JIN Zhiquan, ZHOU Jun, BI Yu′an, WANG Zhenzhong, XIAO Wei. Diterpene ginkgolides meglumine injection attenuates oxygen-glucose deprivation-induced apoptosis of nerve cells via inhibition of calpain signaling pathway[J]. Journal of China Pharmaceutical University, 2015, 46(6): 707-711. DOI: 10.11665/j.issn.1000-5048.20150612
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银杏二萜内酯葡胺注射液通过下调calpain信号通路抑制脑缺血神经细胞凋亡

  • 江苏康缘药业股份有限公司中药制药过程新技术国家重点实验室

基金项目: 国家“重大新药创制”科技部重大专项资助项目(No.2013ZX09402203)；国家重大科技成果转化项目基金资助

Diterpene ginkgolides meglumine injection attenuates oxygen-glucose deprivation-induced apoptosis of nerve cells via inhibition of calpain signaling pathway

摘要

    摘要
  • 摘要: 研究银杏二萜内酯葡胺注射液(diterpene ginkgolides meglumine injection，DGMI)对缺氧缺糖/复氧(oxygen-glucose deprivation/reoxygenation，OGD/R)损伤的人神经母细胞瘤细胞SH-SY5Y凋亡的抑制作用及其机制。采用试剂盒、Fluo-3 AM法、Western blot检测SH-SY5Y细胞氧糖剥离损伤4 h后，与药物一起复氧1 h细胞乳酸脱氢酶(LDH)的漏出量、caspase-3/7酶活力、细胞质中核小体含量、胞浆游离钙离子浓度以及calpain、cleaved caspase-12蛋白量的变化。结果显示DGMI能极显著降低OGD/R损伤的SH-SY5Y细胞LDH的漏出量，抑制caspase-3/7酶活性，减少细胞核核小体的释放量，下调细胞内游离钙离子浓度、calpain和cleaved caspase-12蛋白量，抑制calpain凋亡信号通路保护神经细胞。DGMI对OGD/R诱导的SH-SY5Y细胞凋亡具有显著的抑制作用，其作用机制可能与抑制细胞内Ca2+/calpain/caspase-12/capase-3信号通路有关。
    Abstract: To investigate the anti-apoptotic effect of diterpene ginkgolides meglumine injection(DGMI)on SH-SY5Y cells induced by oxygen-glucose deprivation/reoxygenation(OGD/R), and to explore its mechanisms. After 4 h of OGD, the SH-SY5Y cells were treated with 25 mg/L DGMI for 1 h. The release of lactic dehydrogenase(LDH)was measured by cytotoxicity detection kitplus. Cell apoptosis was detected by caspase-3/7 assays. Cell death was detected by ELISA. The concentration of ［Ca2+］i in cytoplasm was measured by Fluo-3 AM and the levels of calpain and cleaved capaease-12 were evaluated by western blot. As we expected, DGMI significantly decreased the release of LDH, the concentration of ［Ca2+］i, the protein levels of calpain and cleaved caspase-12. Furthermore, DGMI injection also attenuated the activities of caspase-3/7 and the contents of cytoplasmic histone-associated- DNA-fragments. These data demonstrated that the DGMI injection showed good anti-apoptotic effect in SH-SY5Y cells induced by OGD/R. The mechanisms may be associated with the inhibition of Ca2+/calpain/caspase-12/caspase-3 signaling pathway.
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  • 刊出日期:  2015-12-24

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