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

   
@article{APS4081,
	author = {Yi Chang and George Hsiao and Seu-hwa Chen and Yi-cheng Chen and Jiing-han Lin and Kuang-hung Lin and Duen-suey Chou and Joen-rong Sheu},
	title = {Tetramethylpyrazine suppresses HIF-1α, TNF-α, and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats},
	journal = {Acta Pharmacologica Sinica},
	volume = {28},
	number = {3},
	year = {2016},
	keywords = {},
	abstract = {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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/4081}
}