- 學位論文
Cilostazol減輕糖尿病運動神經病變
Cilostazol attenuates diabetic motor neuropathy
摘要
背景：糖尿病神經病變是一種常見且棘手的併發症，有效的治療仍是一大挑戰。糖尿病神經病變相關研究常將重點放在週邊神經的感覺異常，然而，糖尿病運動及中樞神經系統相關的神經病變所知有限且較少以動物實驗評估。 研究目的：本實驗評估糖尿病大鼠生理、生化及運動行為的改變，並評估運動神經及許旺氏細胞的變化。此外，Cilostazol為磷酸二脂酶III的抑制劑，作用為抗血小板及血管舒張的作用，用以評估治療糖尿病神經病變的效果。 實驗方法：雄性SD大鼠隨機分配至三組：正常組(N)、糖尿病組(DM) [股靜脈注射每公斤體重60毫克的鏈脲佐菌素(STZ)]及糖尿病口服Cilostazol組(DM+cilo) [股靜脈注射每公斤體重60毫克的鏈脲佐菌素(STZ)誘導為糖尿病2週後，每日口服每公斤體重100毫克的cilostazol，口服為期6週]。測量水分攝取量、食物攝取量、排出量及體重變化、血糖、三酸甘油脂、總膽固醇等生理生化數值。實驗期間評跑速、跑動距離、足部壓力及坐骨神經功能指數等運動行為。大暑犧牲後評估L5脊髓腹角運動神經表現量、週邊坐骨神經許旺氏細胞及髓鞘蛋白表現量。 結果：糖尿病大鼠造成高血糖、體重減輕、血脂異常及高攝入/排出量。口服給予Cilostazol顯著降低攝入/排出量、三酸甘油脂、總膽固醇，但並不影響血糖及體重變化。糖尿病也導致行走緩慢、高足部壓力及足部蜷縮等運動功能失調，另外，也造成L5脊髓中運動神經、週邊坐骨神經及腹根神經中許旺氏細胞及髓鞘蛋白表現量降低。Cilostazol口服給予後，有效改善運動表現及週邊坐骨神經及腹根神經中許旺氏細胞及髓鞘蛋白表現量，但對L5脊髓中運動神經沒有顯著效果。 結論：Cilostazol口服給予有效減輕糖尿病運動功能失調及週邊神經系統的運動神經病變。
並列摘要
Background: Diabetic neuropathy is the most common and intractable complication and pose great therapeutic challenges. Researches regarding diabetic neuropathy is often ascribed to sensory damage of peripheral nerves, however, information on diabetic neuropathic related to the motor and central nervous system are limited and rarely assess in animal models. Aim:We measured physiological, biochemical, motor behavioural changes, motor neurons and Schwann cells alteration in diabetic rats. Additionally, cilostazol, which inhibits type III phosphodiesterase (PDE), is an antiplatelet agent with a vasodilating action are used to assess the efficacy in the treatment of diabetic neuropathy. Methods: Sprague-Dawlay (SD) rats were divided into three groups: group normal (N); group diabetics (DM) [60 mg/kg streptozotocin (STZ) administration via the right femoral vein] and group diabetes treat with cilostazol (DM+cilo) [STZ-induced DM rats with Cilostazol (100mg/kg) orally administered 2 weeks after STZ- induced diabetes and given daily for six weeks]. Physiological and biochemical changes including intake/output (I/O), weight, plasma glucose, triglyceride and total cholesterol were measured. Motor behavioural tests including running speed, runnung distance, foot pressure and sciatic function index were evaluated. Number of motor neuron cells in L5 spinal ventral horn, proliferation of schwann cell and myelinationin sciatic nerve were assessed Results: Diabetes caused hyperglycemia, weight loss, dyslipidemia and high intake/output (I/O). Cilostazol administration significantly decreased I/O, plasma triglyceride and total cholesterol, but difference on plasma glucose and body weight between group DM and DM+cilo was not found. Diabetes also leads to motor function disorder such as lower running speed, high foot pressure and hindpaw contraction. In addition, diabetes contribute to decrease motor neurons in L5 spinal ventral horn, Schwann cells and myelination in sciatic nerve and ventral root. Cilostazol administration ameliorate motor behavior disorder, alleviate damage of Schwann cells and nerve myelination in ventral root and sciatic nerve, but not significantly effect on motor neuron in L5 spinal ventral horn. Conclusion: Cilostazol administration was effective on attenuation of diabetic motor function disorder and motor neuropathy in peripheral nervous system.
參考文獻
延伸閱讀
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