Tetramethylpyrazine suppresses HIF-1α,TNF-α,and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats  

作　　者：Yi CHANG George HSIAO Seu-hwa CHEN Yi-cheng CHEN Jiing-han LIN Kuang-hung LIN Duen-suey CHOU Joen-rong SHEU 

机构地区：[1]Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 110, Taiwan, China [2]School of Medicine, Fu-Jen Catholic University, Taipei, 110, Taiwan, China [3]Graduate Institute of Medical Sciences, Taipei Medical University, Taipei 110, Taiwan, China

出　　处：《Acta Pharmacologica Sinica》2007年第3期327-333,共7页中国药理学报（英文版）

基　　金：Project supported by grants from the Topnotch Stroke Research Center,Taipei Medical University;the Shin Kong Wu HoSu Memorial Hospital(SKH-TMU-94-07);the Committee on Chinese Medicine and Pharmacy(CCMP 94-RD-031).

摘　　要：Aim： To examine the detailed mechanisms underlying the inhibitory effect of tetramethylpyrazine （TMPZ） in inflammatory and apoptotic responses induced by middle cerebral artery occlusion （MCAO） in rats. Methods： MCAO-induced focal cerebral ischemia in rats was used in this study. The hypoxia-inducible factor-1α （HIF-1α）, activation of caspase-3, and TNF-α mRNA transcription in ischemic regions were detected by immunoblotting and RT-PCR, respectively. Anti-oxidative activity was investigated using a thiobarbituric acid-reactive substance （TBARS） test in rat brain homogenate preparations. Results： We showed the statistical results of the infarct areas of solvent- and TMPZ （20 mg/kg）-treated groups at various distances from the frontal pole in MCAO-induced focal cerebral ischemia in rats. Treatment with TMPZ （20 mg/kg） markedly reduced the infarct area in all regions, especially in the third to fifth sections. MCAO-induced focal cerebral ischemia was associated with increases in HIF-1α and the activation of caspase-3, as well as TNF-α transcription in ischemic regions. These expressions were markedly inhibited by treatment with TMPZ （20 mg/kg）. However, TMPZ （0.5-5 mmol/L） did not significantly inhibit TBARS reaction in rat brain homogenates. Conclusion： The neuroprotective effect of TMPZ may be mediated at least by a portion of the inhibition of HIF-1α and TNF-α activations, followed by the inhibition of apoptosis formation （active caspase-3）, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, TMPZ treatment may represent an ideal approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders.Aim： To examine the detailed mechanisms underlying the inhibitory effect of tetramethylpyrazine （TMPZ） in inflammatory and apoptotic responses induced by middle cerebral artery occlusion （MCAO） in rats. Methods： MCAO-induced focal cerebral ischemia in rats was used in this study. The hypoxia-inducible factor-1α （HIF-1α）, activation of caspase-3, and TNF-α mRNA transcription in ischemic regions were detected by immunoblotting and RT-PCR, respectively. Anti-oxidative activity was investigated using a thiobarbituric acid-reactive substance （TBARS） test in rat brain homogenate preparations. Results： We showed the statistical results of the infarct areas of solvent- and TMPZ （20 mg/kg）-treated groups at various distances from the frontal pole in MCAO-induced focal cerebral ischemia in rats. Treatment with TMPZ （20 mg/kg） markedly reduced the infarct area in all regions, especially in the third to fifth sections. MCAO-induced focal cerebral ischemia was associated with increases in HIF-1α and the activation of caspase-3, as well as TNF-α transcription in ischemic regions. These expressions were markedly inhibited by treatment with TMPZ （20 mg/kg）. However, TMPZ （0.5-5 mmol/L） did not significantly inhibit TBARS reaction in rat brain homogenates. Conclusion： The neuroprotective effect of TMPZ may be mediated at least by a portion of the inhibition of HIF-1α and TNF-α activations, followed by the inhibition of apoptosis formation （active caspase-3）, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, TMPZ treatment may represent an ideal approach to lowering the risk of or improving function in ischemia-reperfusion brain injury-related disorders.

关 键 词：TETRAMETHYLPYRAZINE middle cerebral artery occlusion HIF-1Α CASPASE-3 TNF-Α thiobarbituric acid-reactive substance 

分 类 号：R743.31[医药卫生—神经病学与精神病学]