Effect of cyclosporin a on immediate early gene in rat global ischemia and its neuroprotection.

Effect of cyclosporin a on immediate early gene in rat global ischemia and its neuroprotection.
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DOI:
10.1254/jphs.fp0050799
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发表时间:
2006
影响因子:
3.5
通讯作者:
Tatsuo Yamaguchi;Kazuto Miyata;F. Shibasaki;A. Isshiki;H. Uchino
Tatsuo Yamaguchi;Kazuto Miyata;F. Shibasaki;A. Isshiki;H. Uchino
中科院分区:
医学3区
文献类型:
--
作者:
Tatsuo Yamaguchi;Kazuto Miyata;F. Shibasaki;A. Isshiki;H. Uchino

文献摘要

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用环孢菌素A(cyclosporin A)处理大鼠全脑缺血再灌注后,观察即刻早期基因c-fos和c-jun及其产物蛋白C-FOS、C-JUN和P-JUN在海马CA 1区的表达。对照组动物全脑缺血后7天海马CA 1区神经元死亡率超过90%,而CsA组动物缺血后仅5%细胞死亡。对照组c-fos和c-jun mRNA表达在缺血后1 ~ 48 h逐渐增加。另一方面,它们在CsA处理的动物中显示出显著的抑制。对照组再灌注后1、24和48 h C-FOS表达增加。在CsA治疗的动物中,发现C-FOS表达增加,但表达水平在缺血后48小时内降低至统计学上不显著的水平。C-JUN和P-JUN表达在对照组动物中增加,但在CsA治疗组动物中几乎完全被抑制。本研究表明,CsA对IEG及其产物的抑制作用可能与其对迟发性神经元细胞死亡的显著保护作用有关。
The expressions of the immediate early genes, c-fos and c-jun, and their product proteins C-FOS, C-JUN, and P-JUN were examined in the hippocampal CA1 subfield after global ischemia and reperfusion in rats treated with cyclosporin A. More than 90% neuronal cell death was seen in hippocampal CA1 7 days after global ischemia in control animals, but only 5% cell death after ischemia was seen in the CsA-treated animals. The expressions of c-fos and c-jun mRNA in the control animals were detected with an increase from 1 to 48 h after ischemia. On the other hand, they showed significant suppression in the CsA-treated animals. Increased expressions of C-FOS were found 1, 24, and 48 h after reperfusion in the control animals. In the CsA-treated animals C-FOS expression was found to increase, but the expression level reduced to a statistically insignificant level within 48 h after the ischemia. C-JUN and P-JUN expressions increased in control animals, but were almost completely suppressed in the CsA-treated animals. The present study demonstrated that the suppressant effects of CsA on IEGs and their products might have causal relationship to the dramatic protecting effect of the drug against delayed neuronal cell death.