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七氟醚导致新生大鼠神经元凋亡和适应性变化。

Sevoflurane causes neuronal apoptosis and adaptability changes of neonatal rats.

机构信息

Department of Anesthesiology, Beijing TianTan Hospital, Capital Medical University, Beijing, China; Laboratory of Clinical Medical Research, Beijing TianTan Hospital, Capital Medical University, Beijing, China.

出版信息

Acta Anaesthesiol Scand. 2013 Oct;57(9):1167-74. doi: 10.1111/aas.12163. Epub 2013 Jul 29.

Abstract

BACKGROUND

Neonatal exposure to sevoflurane can induce neurodegeneration and learning deficits in developing brain. We hypothesised that with the increase in the concentration and duration of sevoflurane, neurodegeneration of neonatal rats aggravates and causes behaviour changes as the rats grow.

METHODS

Twenty-one post-natal day (P)7 Wistar rats were randomly divided into seven groups. Blood analysis was performed after anaesthesia. According to the results, 120 P7 Wistar rats were randomly divided into five groups: Con sham anaesthesia; Sevo 1%-2 h: exposed to 1% sevoflurane for 2 h; Sevo 1%-4 h, Sevo 2%-2 h and Sevo 2%-4 h. Caspase-3 positive cells in brain were detected by immunohistochemistry at 6 h after the end of anaesthesia. The cleaved poly(ADP-ribose) polymerase (c-PARP-1) in cortex and hippocampus was detected by Western blot analysis. Behavioural tests such as Morris water maze and Open-field Test were performed when the rats were 5-week old, 8-week old, and 14-week old.

RESULTS

Three per cent sevoflurane induced carbon dioxide accumulation. The level of c-PARP-1 in hippocampus area was significantly increased in Group 2%-4h. The number of caspase-3 positive cells in Group Sevo 1%-2h, Group Sevo 2%-2h and Group Sevo 2%-4h was greater than that in Group Con. Rats exposed to sevoflurane had longer travel distance and time in open field when they were 5 weeks old. Animals from different groups had similar performance in Morris water maze.

CONCLUSION

Exposure to 2% sevoflurane causes neuronal apoptosis of neonatal rats, and long-time exposure aggravates that. The adaptability in new environment is transiently decreased when the anaesthesia rats are 5 weeks old.

摘要

背景

新生鼠接触七氟醚可导致发育期大脑神经退行性变和学习能力下降。我们假设,随着七氟醚浓度和时间的增加,新生大鼠的神经退行性变加重,并导致其生长过程中的行为改变。

方法

21 只出生后 7 天(P)的 Wistar 大鼠被随机分为 7 组。麻醉后进行血液分析。根据结果,将 120 只 P7 Wistar 大鼠随机分为 5 组:Con 假麻醉;Sevo 1%-2 h:暴露于 1%七氟醚 2 h;Sevo 1%-4 h、Sevo 2%-2 h 和 Sevo 2%-4 h。麻醉结束后 6 h 通过免疫组织化学检测脑内 caspase-3 阳性细胞。通过 Western blot 分析检测皮质和海马中的裂解多聚(ADP-核糖)聚合酶(c-PARP-1)。当大鼠 5 周、8 周和 14 周大时,进行 Morris 水迷宫和旷场试验等行为学测试。

结果

3%七氟醚可引起二氧化碳蓄积。2%-4 h 组海马区 c-PARP-1 水平明显升高。Sevo 1%-2 h 组、Sevo 2%-2 h 组和 Sevo 2%-4 h 组的 caspase-3 阳性细胞数均多于 Con 组。暴露于七氟醚的大鼠在 5 周龄时在旷场中的行进距离和时间较长。不同组别的大鼠在 Morris 水迷宫中的表现相似。

结论

暴露于 2%七氟醚可导致新生大鼠神经元凋亡,长时间暴露可加重这种情况。麻醉大鼠在 5 周龄时对新环境的适应性短暂下降。

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