| 摘要: | 腦部缺血所造成的腦組織傷害，尤其是糖尿病患者，其嚴重後遺症是目前臨床治療急須解決的問題。桂枝茯苓丸具有活血化瘀之功效，常被用於婦科疾病之治療。本研究主要目的係觀察桂枝茯苓丸對於正常血糖及streptozotocin (STZ)誘發高血糖老鼠之學習、記憶及腦組織之影響；並探討STZ誘發高血糖老鼠缺血-再灌流腦損傷之中樞神經細胞保護作用。實驗結果顯示：1. 桂枝茯苓丸(1, 2, 4 g/kg)對於STZ所誘發之高血糖小鼠，21天後之體重及血糖，無統計學上的差異；對於小鼠的水迷宮之學習與參考記憶障礙具有明顯的改善作用。2. 桂枝茯苓丸(2, 4 g/kg)減少高血糖大鼠腦組織TUNEL陽性細胞數及caspase-3陽性細胞數，並具統計上之差異。 3. 桂枝茯苓丸(0.25, 0.5, 1 g/kg)對於正常血糖大鼠具有顯著減少腦缺血-再灌流之腦梗塞面積、神經功能缺損及COX-2蛋白質的表現量。4. 桂枝茯苓丸(2, 4 g/kg)對於STZ所誘發之高血糖，或高血糖大鼠腦缺血-再灌流之損傷，均可改善神經功能及減少腦梗面積；並可減低腦組織之caspase-3、增加Bcl-2蛋白質的表現量及減少Bax/Bcl-2 ratio。
從上述結果顯示，桂枝茯苓丸具有改善STZ所誘發高血糖鼠之學習與記憶障礙，並對於STZ所誘發之高血糖大鼠可以減低其腦缺血後之腦損傷及神經細胞凋亡，此作用可能部份經由調節腦組織細胞凋亡相關蛋白質之表現所致。
A clinical distress of treatment for serious sequelae caused by cerebral ischemic brain injury, especially for diabetes patients, is a major issue that needs to be resolved. Guizhi-Fuling-Wan (GFW) has the effects of promoting blood circulation and attenuating swollen plot. In this study, we explored the neuroprotective effect of GFW and its action mechanism. Morris water maze was used for studying the effects of GFW on normal STZ-induced hyperglycemic rodents. Ischemia/reperfusion-induced brain damage was used for studying the neuroprotective effects of GFW on normal STZ-induced hyperglycemic rats. The cerebral ischemia was induced middle cerebral artery and bilateral carotid artery ligation (ischemia/reperfusion).The results were as following:
1. GFW (1, 2, 4 g/kg) did not alter body weight and plasma glucose in STZ-induced hyperglycemic rodents in comparison with STZ group. GFW (2, 4 g/kg) improved spatial memory deficits of Morris water maze in STZ-induced hyperglycemic mice.
2. GFW (1, 2, 4 g/kg) decreased level of caspase-3 protein and increased level of Bcl-2 protein. GFW (2, 4 g/kg) reduced the TUNEL-positive cells and caspase-3 positive cells in STZ-induced hyperglycemic rats.
3. GFW (0.25, 0.5, 1 g/kg) significantly reduced cerebral infarction area, neurological deficits and COX-2 protein expression in ischemia/reperfusion rats.
4. GFW (2, 4 g/kg) could significantly improve cerebral infarction area, and neurological deficits in STZ induced hyperglycemic rats with ischemia/reperfusion brain injury. It increased remarkably in Bcl-2 and decreased in caspase-3 and Bax/Bcl-2 ratio during the protein expression.
In conclusion, GFW has protective effects on the spatial memory deficits and cognition caused by STZ-induced hyperglycemic mice and improves cerebral infarction area and neurological deficits in rat brain injury induced by ischemia/reperfusion in STZ induced hyperglycemic rats. The neuroprotective effects of GFW may be due in part to modulation of the cellular apoptotic protein expression. |
