Kumar Ashwani, Kumar Amit, Jaggi Amteshwar S, Singh Nirmal
Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002 Punjab, India.
Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002 Punjab, India.
Pharmacol Biochem Behav. 2015 Aug;135:20-30. doi: 10.1016/j.pbb.2015.05.006. Epub 2015 May 16.
The present study has been designed to investigate the potential of Cilostazol a phosphodiesterase-3 (PDE-3) inhibitor in diabetes-induced vascular dementia (Vad) employing Wistar rats. A single dose of Streptozotocin (STZ) was used for the induction of diabetes and subsequent Vad in rats. Memory and learning abilities of rats were evaluated with Morris water maze (MWM) test. Serum glucose, body weight, vascular endothelial function, serum nitrite/nitrate levels, brain oxidative stress levels (viz. brain thiobarbituric acid reactive species and reduced glutathione levels), inflammatory markers (viz. brain myeloperoxidase activity and neutrophil infiltration in the brain hippocampal area) and brain acetylcholinesterase activity were also tested. Donepezil was used as positive control. Streptozotocin treated animals showed poor performance on MWM indicating impairment of learning and memory abilities with a significant reduction in body weight, vascular endothelial function, serum nitrite/nitrate levels, along with an increase in serum glucose, brain oxidative stress levels, inflammatory changes and brain acetylcholinesterase activity. Treatment with selective PDE-3 inhibitor, Cilostazol significantly attenuated, diabetes-induced impairment of learning and memory; endothelial dysfunction, and changes in various biochemical parameters. It is concluded that selective PDE-3 inhibitor, Cilostazol may be considered as the potential pharmacological agent for the management of diabetes-induced vascular dementia.
本研究旨在利用Wistar大鼠,研究磷酸二酯酶-3(PDE-3)抑制剂西洛他唑在糖尿病诱导的血管性痴呆(Vad)中的作用潜力。单次注射链脲佐菌素(STZ)用于诱导大鼠糖尿病及随后的Vad。用莫里斯水迷宫(MWM)试验评估大鼠的记忆和学习能力。还检测了血清葡萄糖、体重、血管内皮功能、血清亚硝酸盐/硝酸盐水平、脑氧化应激水平(即脑硫代巴比妥酸反应性物质和还原型谷胱甘肽水平)、炎症标志物(即脑髓过氧化物酶活性和脑海马区中性粒细胞浸润)以及脑乙酰胆碱酯酶活性。多奈哌齐用作阳性对照。链脲佐菌素处理的动物在MWM试验中表现不佳,表明学习和记忆能力受损,体重、血管内皮功能、血清亚硝酸盐/硝酸盐水平显著降低,同时血清葡萄糖、脑氧化应激水平、炎症变化和脑乙酰胆碱酯酶活性增加。用选择性PDE-3抑制剂西洛他唑治疗可显著减轻糖尿病诱导的学习和记忆障碍、内皮功能障碍以及各种生化参数的变化。结论是,选择性PDE-3抑制剂西洛他唑可被视为治疗糖尿病诱导的血管性痴呆的潜在药物。