银杏二萜内酯葡胺注射液通过抑制p38/p53通路保护氧糖剥夺SY5Y细胞的机制  

Involvement of p38-p53 signal pathway in neuroprotective effects of DGMI on SH-SY5Y cells damaged by oxygen-glucose deprivation

作　　者：李雪珂[1,2] 刘秋[3,2] 许治良[3,2] 周军[3,2] 曹亮[3,2] 丁岗[3,2] 王振中[3,2] 萧伟[1,3,2] 

机构地区：[1]南京中医药大学,江苏南京210000 [2]中药制药过程新技术国家重点实验室,江苏连云港222001 [3]江苏康缘药业股份有限公司

出　　处：《中国药理学通报》2016年第12期1699-1704,共6页Chinese Pharmacological Bulletin

基　　金：国家科技部"重大新药创制"科技重大专项资助项目(No2013ZX09402203)

摘　　要：目的探讨银杏二萜内酯葡胺注射液(diterpene ginkgolides meglumine injection,DGMI)对缺糖/缺氧损伤(oxygen-glucose deprivation,OGD)的人神经母细胞瘤细胞(SY5Y)保护的作用及可能的机制。方法 SY5Y细胞OGD损伤4 h后,予药物复氧1 h,然后测定细胞存活率(CCK-8法)、凋亡坏死比率、线粒体膜电位(ΔΨm);蛋白质免疫印迹检测细胞中p-p38、p-p53、Bcl-2、Bax和cleaved caspase-9、cleaved caspase-3蛋白量的变化。结果 DGMI能明显提高OGD损伤的SY5Y细胞的存活率,降低细胞凋亡比率,挽救下降的线粒体膜电位(ΔΨm)。下调p-p38、p-p53、Bax/Bcl-2、cleaved caspase-9、cleaved caspase-3等蛋白量,抑制p38和p53活性,保护神经细胞。结论DGMI对OGD损伤的SY5Y细胞具有明显的保护作用,其保护机制可能与细胞内p38/p53/Bcl-2/caspase-9/caspase-3信号通路的抑制有关。Aim To investigate the protective effects of Diterpene Ginkgolides Meglumine Injection（ DGMI） on SY5 Y cells damaged by oxygen-glucose deprivation and its functional mechanisms. Methods After 4 h of OGD,the cells were treated with 25 mg·L^-1 drugs for1 h. Subsequently,cell viabilities were measured by cell counting kit-8（ CCK-8 kit） and cell apoptosis was measured by flow cytometric analysis. Furthermore,the mitochondrial membrane potential was detected by rhodamine123 staining. The levels of phospho-p38,phospho-p53, Bcl-2, Bax and cleaved caspase-9 /3were evaluated by western blot. Results DGMI significantly increased the cell viabilities of SY5 Y cells damaged by OGD,and reduced OGD-elicited dissipation of mitochondrial membrane potential and cell apoptosis.Furthermore,DGMI also reduced p-p38,p-p53,Bax /Bcl-2 ratio,cleaved caspase-9 and cleaved caspase-3.Conclusion DGMI shows good neuroprotective effects on SY5 Y cells after oxygen-glucose deprivation. The underlying mechanisms may be associated with the suppression of p38 / p53 / Bcl-2 / caspase-9 / caspase-3 signaling pathway.

关 键 词：银杏二萜内酯葡胺注射液 氧糖剥夺 细胞凋亡 P38 P53 Bax/Bcl-2 

分 类 号：R282.71[医药卫生—中药学] R329.25[医药卫生—中医学]