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
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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 17β estradiol group(D_1, D_2 and D_3 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 D_1, D_2 and D_3 groups were intraperitoneally injected with 300, 600 and 900 μg/kg 17β estradiol, respectively. After 30 min, propofol was intraperitoneally injected. The respiratory rate(R_0, R_(30), R_(60), R_(90)), escape latency(T_(D1), T_(D2), T_(D3), T_(D4), T_(D5)), 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 D_1, D_2 and D_3 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 D_1, D_2 and D_3 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 D_1 group, the D_2 group and the D_3 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 D_1 and D_2, D_3, 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 p38 MAPK signaling pathway.
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 17β estradiol group(D_1, D_2 and D_3 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 D_1, D_2 and D_3 groups were intraperitoneally injected with 300, 600 and 900 μg/kg 17β estradiol, respectively. After 30 min, propofol was intraperitoneally injected. The respiratory rate(R_0, R_(30), R_(60), R_(90)), escape latency(T_(D1), T_(D2), T_(D3), T_(D4), T_(D5)), 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 D_1, D_2 and D_3 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 D_1, D_2 and D_3 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 D_1 group, the D_2 group and the D_3 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 D_1 and D_2, D_3, 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 p38 MAPK signaling pathway.
引文
[1] 黄静. 异丙酚对发育期小鼠大脑海马齿回及周边皮质区神经干细胞的影响[D]. 第三军医大学, 2015.
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[14] 王贤军.雌二醇对Aβ25-35诱导海马新生神经元损害的保护作用及其分子机制研究[D].山东大学,2016.
[15] 王强.异氟烷致新生大鼠认知功能障碍与海马P38MAPK通路的关系及其机制研究[D].第二军医大学,2011.
[16] 于淼, 杨万超, 李文志. 蛋白激酶C信号通路在血脑屏障损伤中的研究进展[J]. 疑难病杂志, 2016, 15(2):209-212.
[17] 张晓一, 于潇华, 刘玉环,等. ERK1/2和p38MAPK在介导CGRP和Ang Ⅱ诱导血管平滑肌细胞Nox1表达中的作用[J]. 中国临床药理学与治疗学, 2017, 22(1):13-19.
[18] 王抒, 孙兰, 杜冠华. p38MAPK-控制阿尔采末病进程的新靶点[J]. 中国药理学通报, 2004, 20(5):595-598.
[19] 胡瑾. 细胞凋亡因子表达与神经系统变性疾病相关性研究[J]. 创伤与急危重病医学, 2018,6(3):144-146.
[20] Banki E, Kovacs K, Nagy D, et al. Molecular mechanisms underlying the nephroprotective effects of PACAP in diabetes.[J]. J Mol Neurosci, 2014, 54(3):300-309.
[2] 杨剑, 刘婷婷, 熊兴龙,等. 右美托咪定预处理对异丙酚诱导发育期大鼠离体海马神经细胞损伤的影响[J]. 山东医药, 2017, 57(42):29-31.
[3] 孙玉华, 贺维亚. 17β-雌二醇对血管性痴呆大鼠海马CA1区神经突触可塑性的影响[J]. 中国实用神经疾病杂志, 2010,13(17):22-24.
[4] 李建立,吴红海,史海水, 等.17β雌二醇对氯胺酮诱导发育期大鼠神经细胞凋亡的影响[J].临床麻醉学杂志,2015,31(8):806-808.
[5] 陈建勇, 王聪, 王娟,等. MAPK信号通路研究进展[J]. 中国医药科学, 2011, 1(8):32-34.
[6] 廖朝霞,王飞,曹德雄, 等.p38 MAPK 信号通路在异氟醚诱导新生大鼠海马神经细胞凋亡的作用[J].中国药理学通报,2014,30(12):1661-1666.
[7] 张勤, 罗佛全, 赵为禄,等. 孕早期长时间异丙酚麻醉对子代大鼠认知功能的影响[J]. 中华麻醉学杂志, 2014, 34(9):1051-1053.
[8] 张浩,夏艳萍,陈克研,等.异丙酚作用于孕中期大鼠对子代鼠学习记忆能力的影响[J].沈阳药科大学学报,2016,33(08):647-651.
[9] 惠新晨. 17β-雌二醇和GPR30的选择性激动剂G1在小鼠CA/CPR模型中的神经保护作用研究[D]. 东南大学, 2015.
[10] 王迅, 冷晓磊, 矫永庆,等. 17β雌二醇对大鼠创伤性脑损伤的保护作用[J]. 中国比较医学杂志, 2015, 25(4):23-26.
[11] 包义君. 17β雌二醇在创伤性脑损伤后不同时期分别经非基因组和基因组效应对脑挫裂伤外周水肿带细胞凋亡的保护作用[D]. 中国医科大学, 2012.
[12] 王建平, 张芳芳, 刘春岭,等. 不同剂量17β-雌二醇对血管性痴呆大鼠的神经保护作用[J]. 中国脑血管病杂志, 2008, 5(2):64-69.
[13] 刘兴宇,甄艳凤,崔建忠, 等.MAPKs阻滞剂U0126对创伤性脑损伤大鼠学习记忆功能的影响及机制探讨[J].山东医药,2016,56(18):21-24.
[14] 王贤军.雌二醇对Aβ25-35诱导海马新生神经元损害的保护作用及其分子机制研究[D].山东大学,2016.
[15] 王强.异氟烷致新生大鼠认知功能障碍与海马P38MAPK通路的关系及其机制研究[D].第二军医大学,2011.
[16] 于淼, 杨万超, 李文志. 蛋白激酶C信号通路在血脑屏障损伤中的研究进展[J]. 疑难病杂志, 2016, 15(2):209-212.
[17] 张晓一, 于潇华, 刘玉环,等. ERK1/2和p38MAPK在介导CGRP和Ang Ⅱ诱导血管平滑肌细胞Nox1表达中的作用[J]. 中国临床药理学与治疗学, 2017, 22(1):13-19.
[18] 王抒, 孙兰, 杜冠华. p38MAPK-控制阿尔采末病进程的新靶点[J]. 中国药理学通报, 2004, 20(5):595-598.
[19] 胡瑾. 细胞凋亡因子表达与神经系统变性疾病相关性研究[J]. 创伤与急危重病医学, 2018,6(3):144-146.
[20] Banki E, Kovacs K, Nagy D, et al. Molecular mechanisms underlying the nephroprotective effects of PACAP in diabetes.[J]. J Mol Neurosci, 2014, 54(3):300-309.