Rationale

Vascular dementia (VaD) is the second leading cause of dementia worldwide. It is very important to find the possible pharmacological agents which may be useful in management and therapy of VaD.

Objectives

The present study investigates the effect of ozagrel, a selective thromboxane A2 (TXA2) synthase inhibitor, in a rat model of VaD.

Methods

Single intraperitoneal injection of streptozotocin [STZ, (50 mg/kg)] was administered to Wistar rats to induced diabetes-associated vascular endothelial dysfunction and memory impairment. Morris water maze (MWM) test was employed to assess learning and memory. Endothelial dysfunction was assessed in the isolated aorta by observing endothelial-dependent vasorelaxation and levels of serum nitrite. Various biochemical and histopathological estimations were also performed.

Results

STZ treatment produced endothelial dysfunction, impairment of learning and memory, reduction in body weight and serum nitrite/nitrate, and increase in serum glucose, brain oxidative stress (increased brain thiobarbituric acid reactive species and decreased reduced glutathione levels), brain acetylcholinesterase activity and brain myeloperoxidase activity. Further a significant rise in brain tumor necrosis factor-α & interleukin-6 levels and brain neutrophil infiltration were also observed. Treatment of ozagrel (10 & 20 mg/kg, p. o.)/donepezil (0. 5 mg/kg, i.p., serving as standard) ameliorated STZ induced endothelial dysfunction; memory deficits; biochemical and histopathological changes.

Conclusions

It may be concluded that ozagrel markedly improved endothelial dysfunction; learning and memory; biochemical and histopathological alteration associated with STZ induced dementia and that TXA2 can be considered as an important therapeutic target for the management of VaD.

中文翻译：

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血栓素 A2 合酶抑制可改善链脲佐菌素糖尿病诱导痴呆大鼠模型的内皮功能障碍、记忆缺陷、氧化应激和神经炎症

基本原理

血管性痴呆（VaD）是全球痴呆的第二大原因。找到可能对 VaD 的管理和治疗有用的可能的药物制剂是非常重要的。

目标

本研究调查了选择性血栓素 A2 (TXA2) 合酶抑制剂奥扎格雷在 VaD 大鼠模型中的作用。

方法

单次腹腔注射链脲佐菌素 [STZ, (50 mg/kg)] 给予 Wistar 大鼠以诱导糖尿病相关的血管内皮功能障碍和记忆障碍。莫里斯水迷宫（MWM）测试用于评估学习和记忆。通过观察内皮依赖性血管舒张和血清亚硝酸盐水平来评估离体主动脉的内皮功能障碍。还进行了各种生化和组织病理学评估。

结果

STZ 治疗产生内皮功能障碍、学习和记忆障碍、体重和血清亚硝酸盐/硝酸盐降低、血清葡萄糖增加、脑氧化应激（脑硫代巴比妥酸反应性物质增加和谷胱甘肽水平降低）、脑乙酰胆碱酯酶活性和脑髓过氧化物酶活性。还观察到脑肿瘤坏死因子-α 和白细胞介素 6 水平和脑中性粒细胞浸润的进一步显着升高。ozagrel (10 & 20 mg/kg, p. o.)/donepezil (0. 5 mg/kg, ip , as standard) 的治疗改善了 STZ 诱导的内皮功能障碍；记忆缺陷；生化和组织病理学变化。

结论

可以得出结论，奥扎格雷显着改善了内皮功能障碍；学习和记忆；生化和组织病理学改变与 STZ 诱导的痴呆症相关，并且 TXA2 可被视为治疗 VaD 的重要治疗靶点。