17β雌二醇对异丙酚诱导发育期大鼠海马神经细胞凋亡时p38MAPK信号传导通路的作用机制  

Mechanism of 17β-estradiol on p38MAPK signal transduction pathway in propofol-induced hippocampal neuronal apoptosis in developing rats

作　　者：杜天平 孟祖东 DU Tianping;MENG Zudong(Department of Neurosurgery,People's Hospital Affiliated to Hubei Medical College,Shiyan 420000,Hubei,China;Department of Dermatology,People's Hospital Affiliated to Hubei Medical College,Shiyan 420000,Hubei,China)

机构地区：[1]湖北医药学院附属人民医院神经外科 [2]湖北医药学院附属人民医院(湖北省十堰市人民医院)皮肤科

出　　处：《中国临床药理学与治疗学》2019年第2期128-133,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：湖北省教育厅科研项目(B2014048)

摘　　要：目的:探讨17β雌二醇对异丙酚诱导的发育期大鼠海马神经细胞凋亡的作用机制。方法:将60只发育期SD大鼠随机分为5组:空白对照组(NS组)、异丙酚组(P组)、17β雌二醇组(D_1、D_2及D_3组),每组12只。NS组腹腔注射等体积脂肪乳,P组仅腹腔注射异丙酚;D_1、D_2及D_3组腹腔注射300、600及900μg/kg 17β雌二醇,30 min后腹腔注射异丙酚。观察大鼠的呼吸频率(R_0、R_(30)、R_(60)、R_(90))、逃避潜伏期时间(T_(D1)、T_(D2)、T_(D3)、T_(D4)、T_(D5))、海马神经细胞凋亡指数(AI)及cleaved caspase-3、p-p38及p-NF-κB蛋白表达水平。结果:同NS组比较,P组大鼠注射异丙酚后呼吸频率加快;同P组比较,D_1组、D_2组、D_3组呼吸频率减慢(P<0.05)。P组大鼠逃避潜伏期显著长于NS组,D_1组、D_2组、D_3组逃避潜伏期显著低于P组(P<0.05)。P组大鼠AI显著高于NS组,D_1组、D_2组、D_3组显著低于P组(P<0.01)。同NS组比较,P组cleaved caspase-3、p-p38及其下游p-NF-κB表达增加(P<0.01);同P组比较,D_1组及D_2、D_3组cleaved caspase-3、p-p38及其下游p-NF-κB表达下调(P<0.01)。结论:17β雌二醇可减轻异丙酚诱导的大鼠海马神经细胞凋亡,其作用机制可能与抑制p38MAPK信号传导通路有关。AIM:To investigate the mechanism of 17β-estradiol on the apoptosis of rat hippocampal neurons induced by propofol.METHODS:Sixty SD rats were randomly divided into 5 groups:control group(NS group),propofol group(P group)and 17βestradiol group(D1,D2 and D3 groups),with 12 rats in each group.The rats in the NS group were intraperitoneally injected with equal volume of fat emulsion.The rats in the P group were only intraperitoneally injected with propofol.The rats in the D1,D2 and D3 groups were intraperitoneally injected with 300,600 and 900μg/kg 17βestradiol,respectively.After 30 min,propofol was intraperitoneally injected.The respiratory rate(R 0,R 30,R 60,R 90),escape latency(TD1,TD2,TD3,TD4,TD5),hippocampal neuronal apoptosis index(AI)and cleaved caspase-3,p-p38 and p-NF-κB protein expression level were observed.RESULTS:Compared with the NS group,the respiratory rate of the rats in the P group was increased after the injection of propofol(P<0.05).Compared with the P group,the respiratory rate of the D1,D2 and D3 groups was slower(P<0.05).The escape latency of rats in group P was significantly longer than that in NS group(P<0.05).The escape latency of group D1,D2 and D3 was significantly lower than that of group P(P<0.05).The AI of the rats in the P group was significantly higher than that in the NS group,and the D1 group,the D2 group and the D3 group were significantly lower than the P group(P<0.01).Compared with NS group,the expression of cleaved caspase-3,p-p38 and its downstream p-NF-κB increased in group P(P<0.01).Compared with group P,group D1 and D2,D3,the expression of p-p38,cleaved caspase-3 and its downstream p-NF-κB was down-regulated(P<0.01).CONCLUSION:17β-estradiol can alleviate the apoptosis of rat hippocampal neurons induced by propofol,and its mechanism may be related to the inhibition of p38MAPK signaling pathway.

关 键 词：17Β雌二醇 异丙酚 大鼠 海马 P38MAPK 

分 类 号：R965.2[医药卫生—药理学] R614[医药卫生—药学]