p90RSK/Bcl-2信号通路在异丙酚逆转谷氨酸诱发的大鼠星型胶质细胞毒性中的作用  

The effect of p90RSK/Bcl-2 signaling pathway in propofol reversing glutamate-induced astrocyte cytotoxicity in rats

作　　者：覃银莹 关睿聪 李春来 肖飞[1] 潘嗣宁[1] 谢玉波[1] Qin Yinying;Guan Ruicong;Li Chunlai;Xiao Fei;Pan Sining;Xie Yubo(Anesthesiology Department,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学第一附属医院麻醉科,南宁530021

出　　处：《广西医科大学学报》2020年第9期1605-1609,共5页Journal of Guangxi Medical University

基　　金：广西重点研发计划资助项目(No.桂科AB18221031);国家自然科学基金资助项目(No.81373498)。

摘　　要：目的:探讨p90RSK/Bcl-2信号通路在异丙酚逆转谷氨酸诱发的大鼠星型胶质细胞毒性中的作用及机制。方法:体外培养原代星形胶质细胞至第7天,按随机数字表法分为对照组(C组)、异丙酚组(P组)、谷氨酸组(G组)、抑制剂组(I组)、异丙酚+谷氨酸组(PG组)和异丙酚组+谷氨酸+抑制剂组(PGI组),每组12例。C组不做任何处理,P组、G组和I组分别用100μmol/L异丙酚孵育6 h、3.5 mmol/L谷氨酸孵育6 h和10μmol/L p90RSK抑制剂LJH685孵育30 min,PG组先用100μmol/L异丙酚孵育6 h后用3.5 mmol/L谷氨酸孵育6 h,PGI组先用10μmol/L LJH685孵育30 min,后同PG组。采用CCK-8法检测各组星形胶质细胞的活力,Western blot法检测活化caspase-3、Bcl-2、Bax和p90RSK的蛋白表达水平,AnnexinⅤ-PI凋亡试剂盒检测各组细胞凋亡情况,qPCR法检测各组Bcl-2mRNA的表达水平。结果:与C组比较,G组和I组星形胶质细胞的活力下降、凋亡率明显升高,活化caspase-3和Bax表达上调,Bcl-2和p90RSK表达下调(P<0.05);与PG组比较,G组和PGI组星形胶质细胞的活力下降、凋亡率明显升高,活化caspase-3和Bax表达上调,Bcl-2和p90RSK表达下调(P<0.05)。结论:异丙酚逆转谷氨酸诱发的大鼠星型胶质细胞毒性中的机制可能与激活p90RSK/Bcl-2信号通路有关。Objective:To explore the effect and mechanism of p90RSK/Bcl-2 signal pathway in propofol reversing glutamate-induced astrocyte toxicity in rats.Methods:Primary astrocytes were cultured in vitro until day 7,and were randomly divided into control group(group C),propofol group(group P),glutamate group(group G),inhibitor group(group I),propofol+glutamate group(groupPG)and propofol+glutamate+inhibitor group(groupPGI)according to random number table,with 12 cases in each group.Group Cdid not give any treatment.GroupP,groupG,and groupI were incubated with 100μmol/L propofol for 6 h,3.5 mmol/L glutamic acid for 6 h,and 10μmol/L p90RSK inhibitor LJH685 for 30 min,respectively.PG group was incubated with 100μmol/L propofol for 6 h and then incubated with 3.5 mmol/L glutamic acid for 6 h.PGI group was incubated with 10μmol/L LJH685 for 30 min,and then the steps were the same as PG group.The activity of astrocytes in each group was detected by CCK-8 method.The protein expression levels of activated caspase-3,Bcl-2,Bax,and p90RSK were detected byWestern blot.Apoptosis in each group was detected by Annexin V-PI apoptosis kit.The mRNA expression level of Bcl-2 in each group was detected by qPCR method.Results:Compared with group C,the activity of astrocytes was decreased,the apoptosis rate was significantly increased,the expression of activated caspase-3 and Bax was up-regulated,and the expression of Bcl-2 and p90RSK was down-regulated in group G and group I(P<0.05).Compared with group PG,the activity of astrocytes was decreased,the rate of apoptosis was significantly increased,the expression of activated caspase-3 and Bax was up-regulated,and the expression of Bcl-2 and p90RSK was down-regulatedin group G and groupPGI (P<0.05).Conclusion:The mechanism of propofol reversing glutamate-induced astrocytetoxicity may be related to the activation of p90RSK/Bcl-2 signal pathway.

关 键 词：异丙酚 谷氨酸 星形胶质细胞 神经毒性 

分 类 号：R614.1[医药卫生—麻醉学]