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首页> 外文期刊>Planta medica: Natural products and medicinal plant research >Inhibitory mechanisms of tetramethylpyrazine in middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats.
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Inhibitory mechanisms of tetramethylpyrazine in middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats.

机译：川methyl嗪对大脑中动脉闭塞（MCAO）所致大鼠局灶性脑缺血的抑制机制。

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摘要

Tetramethylpyrazine (TMPZ) is an active ingredient isolated from a commonly used Chinese herb, Ligusticum wallichii Franchat, which has long been used in China for the treatment of vascular diseases. In the present study, TMPZ significantly attenuated middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats. Administration of TMPZ at 10 and 20 mg/kg produced concentration-dependent reductions in infarct size compared to that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in both nitrotyrosine and inducible nitric oxide synthase (iNOS) expression in ischemic regions. The expressions of nitrotyrosine and iNOS were markedly inhibited by TMPZ (20 mg/kg) treatment. Furthermore, TMPZ (100-250 microM) concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by fMLP (800 nM) and PMA (320 nM). TMPZ (100-250 microM) also significantly inhibited neutrophil migration stimulated by fMLP (800 nM) and LTB4 (160 nM). An electron spin resonance (ESR) method was used to further study the scavenging activity of TMPZ on free radicals formed in human neutrophils. TMPZ (100 and 200 microM) greatly reduced the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate a neuroprotective effect of TMPZ in MCAO-induced focal cerebral ischemia in vivo. TMPZ mediates at least part of the free radical-scavenging activity and inhibits neutrophil activation, 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.
机译：川methyl嗪（TMPZ）是从常用中草药​​女贞（Ligusticum wallichii Franchat）中分离出来的活性成分，该草药在中国长期以来一直用于治疗血管疾病。在本研究中，TMPZ显着减轻大鼠大脑中动脉闭塞（MCAO）引起的局灶性脑缺血。与对照大鼠相比，以10和20 mg / kg的剂量施用TMPZ可使梗死面积呈浓度依赖性降低。 MCAO诱导的局灶性脑缺血与缺血区域中硝基酪氨酸和诱导型一氧化氮合酶（iNOS）表达的增加有关。 TMPZ（20 mg / kg）处理可明显抑制硝基酪氨酸和iNOS的表达。此外，TMPZ（100-250 microM）浓度依赖性地抑制了由fMLP（800 nM）和PMA（320 nM）刺激的人类嗜中性粒细胞的呼吸爆发。 TMPZ（100-250 microM）还显着抑制fMLP（800 nM）和LTB4（160 nM）刺激的嗜中性粒细胞迁移。电子自旋共振（ESR）方法用于进一步研究TMPZ对人类嗜中性粒细胞中形成的自由基的清除活性。 TMPZ（100和200 microM）大大降低了羟基自由基形成的ESR信号强度。总之，我们证明了TMPZ在MCAO诱导的局灶性脑缺血体内具有神经保护作用。 TMPZ介导至少一部分清除自由基的活性并抑制中性粒细胞的活化，从而导致缺血再灌注脑损伤的梗塞体积减少。因此，TMPZ治疗可能是降低缺血再灌注脑损伤相关疾病的风险或改善其功能的理想方法。

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