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.
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Project supported by grants from the Topnotch Stroke Research Center, Taipei Medical University; the Shin Kong Wu Ho Su Memorial Hospital (SKH-TMU-94-07) and the Committee on Chinese Medicine and Pharmacy (CCMP 94-RD-031).
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Chang, Y., Hsiao, G., Chen, Sh. et al. Tetramethylpyrazine suppresses HIF-1α, TNF-α, and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats . Acta Pharmacol Sin 28, 327–333 (2007). https://doi.org/10.1111/j.1745-7254.2007.00514.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00514.x
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