Tetramethylpyrazine suppresses the HIF-1;  TNF-;  and active caspase-3 expressions in middle cerebral artery occlusion-induced brain ischemia in rats

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Title:	Tetramethylpyrazine suppresses the HIF-1;TNF-;and active caspase-3 expressions in middle cerebral artery occlusion-induced brain ischemia in rats
Authors:	許準榕 Chang Y;Hsiao G;Chen YC;Lin JH;Lin KH;Chou DS;Sheu JR
Contributors:	醫學科學研究所
Date:	2007
Issue Date:	2009-08-25 09:56:36 (UTC+8)
Abstract:	Tetramethylpyrazine suppresses the HIF-1a, TNF-a, and active caspase-3 expressions in middle cerebral artery occlusion-induced brain ischemia in rats 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-1alpha(HIF-1alpha), activation of caspase-3, and TNF-alpha 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-1alpha and the activation of caspase-3, as well as TNF-alpha 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-1alpha and TNF-alpha 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.
Relation:	Acta Pharmacol. Sin.(28):327-333.
Data Type:	article
Appears in Collections:	[Graduate Institute of Medical Sciences] Periodical Article

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