桃紅四物湯併用血栓溶解劑rt-PA在大鼠血栓誘導缺血性中風的研究

中風一直是名列國人十大死因前三的重大疾病之一，其中缺血性中風占七成之多，而缺血性中風造成的傷害除了來自於梗塞期局部腦缺氧的傷害，中風後產生的血液再灌流所造成的傷害加成常常是中風病人在積極治療後死亡的主因；而中大腦動脈栓塞是常使用的模擬此傷害進程的疾病模式。　在中風後黃金搶救期三小時內，目前最廣泛、也具有良好療效的治療用藥為靜脈注射rt-PA，但rt-PA的注射也伴隨顱內出血的副作用，提高死亡風險，在治療缺血性中風中成了一大隱憂。　桃紅四物湯在傳統醫學上是常見的活血化瘀的複方，其中紅花，川芎等單方已有報導指出可抑制血小板凝集及降低大腦腫脹體積有顯著的效用，對於腦血管疾病有一定的治療效果，而在本實驗室之前的研究指出，桃紅四物湯具有良好神經保護的功能。　本實驗評估的方向便是利用大鼠自體血栓後引發中大腦動脈栓塞的缺血性中風模式，探討病症發生前預先投藥影響腦組織產生的缺血承受性的提高，以及病症發生後積極性治療所產生的協同效應。實驗結果顯示，桃紅四物湯併用rt-PA ( 4mg/kg ) 能夠有意義地改善因缺血再灌流傷害所引起之行為能力下降及減少梗塞面積，組織染色顯示可減少細胞凋亡以及壞死情況；投與桃紅四物湯併用rt-PA能夠減少iNOS的表現，且發現nitrotyrosine的產量受到抑制，證實桃紅四物湯併用rt-PA ( 4mg/kg )具有抗發炎效果，而利用TUNEL staining的結果顯示細胞凋亡現象可被明顯改變；此次實驗指出桃紅四物湯併用rt-PA ( 4mg/kg )的組別能提升腦部缺血的容忍能力，以及神經保護功能。

關鍵字

腦中風；桃紅四物湯；血栓；神經保護功能；缺血容忍能力

並列摘要

Stroke is the primary cause of the mortality and morbidity worldwide, ischemic stroke is especially occurred the greatly number of the part. It involves many molecular and physiologic pathway get harmful hurts in brain from local brain area hypoxia to cerebrovascular reperfusion, It’s the reasons why after positive therapy, Stroke patients might paralysis or lethal. The middle cerebral artery is the vessel mostly affected by cerebral occlusion in ischemic stroke, thus the middle cerebral artery occlusion (MCAO) of rodents provides an excellent model to mimic human ischemic stroke. In the period of initiate therapy within ＜ 3 hours after stroke onset, injection rt-PA to resolve embolus and recover cerebrovascular blood flow is the widely and effectively strategy of therapy stroke. Unfortunately, according recently reports, rt-PA might get side-effects like ICH (intracerebral hemorrhage), it’s hardly to overcome phenomenon in deal with stroke patient. Tao-Hong-Si-Wu-Tang (THSWT), a multi-traditional herbal medicine, had been shown to improve microcirculation of cardial and cerebral diseases. Each compositions had been reported their functions like Hong-Hua(Carthamus tinctorius)、rhizoma chuanxiong can inhibit platelet aggregation and decrease brain infract volume. However, this multi-herbal medicine had no related study present. In this study, we investigated the synergic effects which combined THSWT and rt-PA are enhanced brain ischemic tolerance and neuronprotection. Our results indicates that better neurological scores, smaller infarct area and smaller infarct volume were noted in the treatment of THSWT (0.7g/kg/day, oral administration) and rt-PA (4mg/kg, intravenous) group. Furthermore, the therapy strategy is provided anti-inflammation effect with significantly reduced iNOS expression and oxidative stress production (nitrotyrosine); Moreover, it suggests anti-apoptosis effect that TUNEL staining significantly attenuated compare with only MCAO surgery group.

並列關鍵字

stroke ； thromobus ； THSWT ； rt-PA ； neruonprotection ； ischemic tolerance ； anti-inflammation ； anti-apoptosis ； iNOS ； nitrotyrosine

參考文獻

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桃紅四物湯併用血栓溶解劑rt-PA在大鼠血栓誘導缺血性中風的研究

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