生長因子：腦中風治療的明日之星

Growth factors: The Future of Ischemic Stroke Therapy

腦中風（cerebrovascular stroke） 一直威脅著人類生命，腦中風可分為缺血性腦中風 ischemic stroke） 與出血性腦中風（hemorrhagic stroke），而大多數屬於後者。腦中風不但位居台灣十大死亡原因的前三名，而且所造成個人殘疾也使社會與家庭付出大量心力，同時造成醫療資源的嚴重支出。幾千年來醫家長期與腦中風奮鬥，有些以前的療法仍沿用至今，如放血、活血化瘀的草藥方劑及針灸等等；新近的療法有urokinase、streptokinase 及t-PA，雖有一定的效果但是總不能滿意。在動物及人類神經細胞培養對缺血性的傷害研究發現細胞會啟動細胞內與細胞間的訊息傳遞以抗拒細胞退化與死亡。腦傷害誘發許多不同的生長因子或細胞激素（cytokines） 來保護細胞，勿使細胞遭受缺血性病理變化如興奮性毒性（excitotoxicity）、缺氧（hypoxia）、低血糖與過氧化物的侵擾。神經保護訊息傳遞促成細胞離子的恒定，抑制自由基的堆積。本文特闡述神經滋養因子（neurotrophic factor）， 鹼性纖維母細胞生長因子 （basic fibroblast growth factor）、 血管內皮生 長因子（vascular endothelial growth factor） 與乙型轉形生長因子（transforming growth factor β） 對腦梗塞後神經保護作用的機制。這些生長因子均有保護神經細胞避免因為腦損傷而造成的死亡，其作用有神經生長性（neurogenic）、血管生長性（angiogenic）、神經滋養性（neurotrophic）、抑制麩氨酸鹽與NMDA 所引發的興奮性毒性及抗氧化作用，但是這些僅限於動物模式，應用於臨床還有一段艱辛的歷程。若可以一一克服必是另一有利的療法。

Cerebrovascular stroke has threatened human life for a long time, the strokes can be divided into ischemic stroke and hemorrhagic stroke, the latter the most numerous. Cerebrovascular stroke is not only one of the leading three causes death causes in Taiwan, but also the cause of disability resulting in a heavy burden on medical resources. For thousands of years, medical specialists have fought against strokes, there are some ancient therapies we can still see today, such as blood letting, herbs stimulating the circulation of blood and acupuncture, etc. Besides, thrombolytictherapy is popular nowadays, such as urokinase, streptokinase, t-PA, they can achieve some effects but not all. The study of ischemic brain injury in cell culture, animal models, and humans have revealed inter- and intra-cellular signaling pathways that increase resistance to cell degeneration and death. Brain injury induces expression of many different growth factors and cytokines, which can protect neurons against insults relevant to the pathogenesis of ischemic brain injury, including excitoxicity, hypoxia, hypoglycemia, acidosis, and pro-oxidants. Neuroprotective signal transduction pathways elicit changes that promote the maintenance of cellular ion homeostasis and/or suppressed the accumulation of free radicals. This article willdiscuss the mechanism of post-ischemic neuroprotection of growth factors such as neurotrophic factor, basic fibroblast growth fact, vascular endothelial growth factor and transforming growth factor-β. These growth factors have the effects of neurogenesis, angiogenesis, neurotrophy, inhibitory excitoxity induced by glutamate and NMDA, and anti-oxidative, by these ways they can prevent neural cells from death. Although it is a long road to apply them into clinical use, it can be expected to become another powerful therapy if the difficulties are overcome.