Department of Pharmacy, Changzhou No. 2 People's Hospital Affiliated with Nanjing Medical University, China.
J Pharmacol Sci. 2014;124(4):418-26. doi: 10.1254/jphs.13157fp. Epub 2014 Mar 27.
Telmisartan, an angiotensin II type 1-receptor blocker (ARBs), has been reported to exert beneficial effects on the central nervous system (CNS). However, the effect of telmisartan on cognitive impairment associated with type 1 diabetes is not well known. Here, we examined the possibility that telmisartan could improve memory function in a type 1 diabetic mouse model, streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice subjected to the Morris Water Maze (MWM) task exhibited a significant decline of spatial learning and memory. Oral administration of telmisartan at two nonhypotensive doses (0.7 or 0.35 mg/kg) significantly improved memory deficits in STZ-induced diabetic mice. Telmisartan treatment markedly reduced Aβ₄₂, APP, BACE1, RAGE, and NF-κB p65 of the hippocampus and cortex, but did not beneficially affect hyperglycemia and hypoinsulinemia in the STZ-induced diabetic mice compared with untreated diabetic mice. Taken together, our findings suggest that telmisartan ameliorates memory deficits in type 1 diabetic mice, at least partly because of attenuation of amyloidosis in the brain.
替米沙坦是一种血管紧张素 II 型 1 型受体阻滞剂 (ARB)，据报道对中枢神经系统 (CNS) 有有益作用。然而，替米沙坦对 1 型糖尿病相关认知障碍的影响尚不清楚。在这里，我们研究了替米沙坦是否可能改善链脲佐菌素 (STZ)诱导的糖尿病小鼠模型中的记忆功能。STZ 诱导的糖尿病小鼠在水迷宫 (MWM) 任务中表现出明显的空间学习和记忆能力下降。替米沙坦以两种非降压剂量 (0.7 或 0.35mg/kg) 口服给药可显著改善 STZ 诱导的糖尿病小鼠的记忆缺陷。替米沙坦治疗可显著降低海马和皮质中的 Aβ₄₂、APP、BACE1、RAGE 和 NF-κB p65，但与未治疗的糖尿病小鼠相比，对 STZ 诱导的糖尿病小鼠的高血糖和低胰岛素血症没有有益影响。综上所述，我们的研究结果表明，替米沙坦可改善 1 型糖尿病小鼠的记忆缺陷，至少部分原因是减轻了大脑中的淀粉样变性。
