摘要: |
目的: 明确丙泊酚对体外培养的发育期新生小鼠海马神经元释放组织纤溶酶原激活物(tPA)的影响,并进一步探讨加入外源性tPA能否逆转丙泊酚对发育神经元的毒性损伤作用。 方法: 将体外培养的发育期小鼠海马神经元分为4组:对照组(C组)、丙泊酚组(Pro组)、tPA组和丙泊酚+tPA组(Pro+tPA组)。C组不做任何处理;Pro组在培养液中加入丙泊酚,终浓度为5、10、30 μmol/L,继续孵育不同的时间(1 h、2 h、3 h、6 h);tPA组在培养液中加入tPA,终浓度为1 μmol/L,继续孵育6 h;Pro+tPA组在在培养液中同时加入tPA(终浓度1 μmol/L)及丙泊酚(终浓度10 μmol/L),继续孵育6 h。检测各组神经元凋亡率及凋亡指标actived-caspase-3蛋白的表达情况。 结果: Pro组神经元的凋亡率及actived-caspase-3蛋白的表达水平较C组显著上调(P<0.05)。Pro组tPA水平显著低于C组(P<0.05)。Pro+ tPA组的神经元的凋亡率及actived-caspase-3蛋白的表达水平显著低于Pro组(P<0.05)。 结论: 丙泊酚可通过抑制神经元释放tPA而对体外培养的新生小鼠发育期海马神经元产生毒性损伤作用,外源性加入tPA可部分逆转丙泊酚的神经毒性作用。 |
关键词: 丙泊酚 发育期神经元 毒性损伤 |
DOI:10.12025/j.issn.1008-6358.2016.20160117 |
分类号:R971+2 |
文献标识码:A |
基金项目:国家自然科学基金资助项目(编号:81400930);上海市卫生和计划生育委员会青年科学基金项目(编号:20144Y0234);复旦大学附属中山医院青年基金项目(编号:2014ZSQN27);复旦大学附属中山医院优秀青年计划资助项目(编号:2015ZSYXQN19) |
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Propofol Induces Neurotoxicity by Inhibiting tPA Release of Neuronal Synapse in Mouse Hippocampus |
LIANG Chao, CANG Jing, XUE Zhanggang
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Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Abstract: |
Objective: To explore the effect of propofol on the tPA release of hippocampal neurons in developing mice, so as to investigate whether exogenous tPA could reverse the propofol-induced neurotoxicity on developing neurons. Methods: The hippocampal neurons of developing mice cultured in vitro were divided into 4 groups(n=20 each):control group(group C),propofol group(group Pro), group tPA and propofol plus tPA group(group Pro+tPA).There was no specific treatment in group C. In group Pro,propofol was added to the culture media with the final concentration of 5,0, 30 μmol/L, respectively, and the cells were then incubated for 1 h, 2 h, 3 h, 6 h, respectively.In group tPA,tPA was added to the culture media with the final concentration of 1 μmol/L,and the cells were then incubated for 6 h.In group Pro+tPA, both propofol and tPA were added to the culture with the final concentration of 10 μmol/L and 1 μmol/L,respectively, and the cells were then incubated for 6 h.The neuron apoptosis rate and the expression level of actived-caspase-3 protein were detected in each group. Results: Compared with that in group C,the apoptosis rate and the expression level of actived-caspase-3 protein in group Pro significantly increased (P<0.05).The tPA level in group Pro was significantly higher than that in group C(P<0.05). Compared with that in group Pro,the apoptosis rate and the expression level of actived-caspase-3 protein in group Pro+tPA significantly decreased (P<0.05). Conclusions: Propofol induces neurotoxicity on hippocampal neurons of developing mice cultured in vitro by inhibiting neuronal tPA release. And exogenous tPA could partially reverse propofol-induced neurotoxicity. |
Key words: Propofol Developing neurons Neurotoxicity |