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

Aim:To examine the detailed mechanisms underlying the inhibitory effect oftetramethylpyrazine(TMPZ)in inflammatory and apoptotic responses inducedby middle cerebral artery occlusion(MCAO)in rats.Methods:MCAO-inducedfocal cerebral ischemia in rats was used in this study.The hypoxia-induciblefactor-1α(HIF-1α),activation of caspase-3,and TNF-αmRNA transcription inischemic regions were detected by immunoblotting and RT-PCR,respectively.Anti-oxidative activity was investigated using a thiobarbituric acid-reactive sub-stance(TBARS)test in rat brain homogenate preparations.Results:We showedthe statistical results of the infarct areas of solvent-and TMPZ(20 mg/kg)-treatedgroups at various distances from the frontal pole in MCAO-induced focal cerebralischemia in rats.Treatment with TMPZ(20 mg/kg)markedly reduced the infarctarea in all regions,especially in the third to fifth sections.MCAO-induced focalcerebral ischemia was associated with increases in HIF-lαand the activation ofcaspase-3,as well as TNF-αtranscription in ischemic regions.These expressionswere markedly inhibited by treatment with TMPZ(20 mg/kg).However,TMPZ(0.5-5mmol/L)did not significantly inhibit TBARS reaction in rat brain homogenates.Conclusion:The neuroprotective effect of TMPZ may be mediated at least by aportion of the inhibition of HIF-1αand TNF-αactivations,followed by the inhibi-tion of apoptosis formation(active caspase-3),resulting in a reduction in theinfarct volume in ischemia-reperfusion brain injury.Thus,TMPZ treatment mayrepresent an ideal approach to lowering the risk of or improving function in is-chemia-reperfusion brain injury-related disorders.