缺血性中風佔世界十大死因當中的第二名。在台灣，包含中風的腦血管疾病也佔我國十大死因當中的第三名。然而病患患有急性缺血性中風的情況下會伴隨著短暫血壓升高的反應。文獻統計顯示病患遭受急性缺血性中風所造成的升血壓反應會隨著中風後血壓增高程度，對於病患造成癒後不良、二次中風機率上升以及死亡率的增高，因此中風後的血壓調控變成一件重要的事情。而針對中風的研究，文獻指出活化腦中內源性大麻素 (又稱內生性大麻素) 系統可以有效減低中風後腦部損傷之情形，得知內生性大麻素具有保護的功能。而內生性大麻素在先前研究指出可以降低自發性高血壓大鼠的血壓。腦中的室旁核為壓力反應核區，因應壓力調節身體及腦部機能來應對；而穹窿下器官則是感知體液的變動來調節，此兩個核區皆可以調節血壓且同時都有表現內生性大麻素系統。因此本論文的假說為在室旁核與穹窿下器官中的內生性大麻素系統可以降低中風後的升血壓反應。本論文使用小鼠中大腦動脈栓塞作為實驗模式，也觀察到小鼠血壓在中風後4小時與24小時有顯著上升。模式建立之後，我們發現室旁核與穹窿下器官第一型大麻素受體表現量在中風後顯著上升。接著我們想探討在此二核區之第一型大麻素受體之角色，因此外源給予小鼠腦部內源性大麻素成分AEA與2-AG至側腦室，發現可以顯著降低中風後升血壓反應，而機制為活化抗氧化酵素如超氧岐化酶 (superoxide dismutase, SOD) 家族與穀胱甘肽過氧化物酶 (glutathione peroxidase, Gpx) 家族，另外則可以降低環氧化酶2 (cyclooxygenase 2, COX2) 的表現量達到減少發炎反應的結果。為了更確大麻素受體第一型在中風後降血壓的功能，本論文另外使用了大麻素受體第一型同源基因踢除鼠並給予中風手術，發現在中風後其血壓相較於正常老鼠有顯著增加的結果，同時也給予第一型大麻素受體缺陷小鼠AEA與2-AG，發現在第一型大麻素受體缺陷小鼠的血壓在缺血性中風後依然短暫升高，因此可以更證明第一型大麻素受體在中風後的角色為抑制中風後升血壓反應。

In Taiwan, cerebrovascular disease, including stroke, is the third cause of death. However, patients with acute ischemic stroke are usually accompanied with a transient increase of blood pressure after stroke. Statistics show that patients suffering from an increase of blood pressure after ischemic stroke are associated with high recurrence of stroke. Literature shows that the endocannabinoid system (ECS) contributes to alleviate brain injury induced by stroke. Moreover, ECS also suppresses blood pressure in spontaneous hypertensive rat. Therefore, we hypothesized that ECS in the PVN and SFO can prevent transient increased blood pressure after acute ischemic stroke. The middle cerebral artery occlusion (MCAO) was used as an animal model of transient increased blood pressure after ischemic stroke. We found that the cannabinoid receptor type 1 (CB1R) in PVN and SFO was up-regulated after ischemic stroke. Our results indicated that the brain levels of ECS ligand, 2-arachidonoylglycerol (2-AG) in the PVN and SFO was decreased after ischemic stroke. Subsequently, increasing 2-AG and AEA levels in the brain significantly prevented an increase of blood pressure after ischemic stroke. Our results indicated that antioxidant enzymes, in the PVN, were up-regulated in stroked mice after 2-AG infusion into the lateral ventricle. In addition, we found that CB1R knockout mice showed increased systolic blood pressure after ischemic stroke compared with the control group. These results indicated that the endocannabinoid system prevents transient increased blood pressure after acute ischemic stroke through activation of antioxidant enzyme in the PVN and SFO.

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