Ma Xiao-Hui, Gao Qiang, Jia Zhen, Zhang Ze-Wei
1Department of Radiology , and.
Int J Neurosci. 2015 Feb;125(2):140-6. doi: 10.3109/00207454.2014.912217. Epub 2014 May 27.
Hundreds of previous studies demonstrated the cytoprotective effect of trichostatin-A (TSA), a kind of histone deacetylases inhibitors (HDACIs), against cerebral ischemia/reperfusion insult. Meanwhile, phosphatidylinositol-3 kinase/Akt (PI3K/Akt) is a well-known, important signaling pathway that mediates neuroprotection. However, it should be remains unclear whether the neuroprotective capabilities of TSA against cerebral ischemia/reperfusion is mediated by activation of the PI3K/Akt signaling pathway.
Five groups rats (n = 12 each), with middle cerebral artery occlusion (MCAO) except sham group, were used to investigate the neuroprotective effect of certain concentration (0.05 mg/kg) of TSA, and whether the neuroprotective effect of TSA is associated with activation of the PI3K/Akt signaling pathway through using of wortmannin (0.25 mg/kg).
TSA significantly increased the expression of p-Akt protein, reduced infarct volume, and attenuated neurological deficit in rats with transient MCAO, wortmannin weakened such effect of TSA dramatically.
TSA could significantly decrease the neurological deficit scores and reduce the cerebral infarct volume during cerebral ischemia/reperfusion injury, which was achieved partly by activation of the PI3K/Akt signaling pathway via upgrading of p-Akt protein.
此前数百项研究证实，曲古抑菌素A（TSA），一种组蛋白去乙酰化酶抑制剂（HDACIs），对脑缺血/再灌注损伤具有细胞保护作用。同时，磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）是一条众所周知的重要信号通路，介导神经保护作用。然而，TSA对脑缺血/再灌注的神经保护能力是否由PI3K/Akt信号通路的激活介导仍不清楚。
除假手术组外，将五组大鼠（每组n = 12）进行大脑中动脉闭塞（MCAO），以研究一定浓度（0.05 mg/kg）的TSA的神经保护作用，以及TSA的神经保护作用是否通过使用渥曼青霉素（0.25 mg/kg）与PI3K/Akt信号通路的激活相关。
TSA显著增加短暂性MCAO大鼠中p-Akt蛋白的表达，减少梗死体积，并减轻神经功能缺损，渥曼青霉素显著削弱了TSA的这种作用。
TSA可显著降低脑缺血/再灌注损伤期间的神经功能缺损评分并减少脑梗死体积，这部分是通过提高p-Akt蛋白激活PI3K/Akt信号通路实现的。
