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替米沙坦通过减轻脑淀粉样变改善链脲佐菌素诱导的糖尿病小鼠的记忆缺陷。

Telmisartan treatment ameliorates memory deficits in streptozotocin-induced diabetic mice via attenuating cerebral amyloidosis.

机构信息

Department of Pharmacy, Changzhou No. 2 People's Hospital Affiliated with Nanjing Medical University, China.

出版信息

J Pharmacol Sci. 2014;124(4):418-26. doi: 10.1254/jphs.13157fp. Epub 2014 Mar 27.

Abstract

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.

摘要

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。

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