Learning and memory deficits are obvious symptoms that develop over time in patients with poorly controlled diabetes. Hyperactivity of the renin-angiotensin system (RAS) is directly associated with β-cell dysfunction and diabetic complications, including cognitive impairment. Here, we investigated the protective and molecular effects of two RAS modifiers, aliskiren; renin inhibitor and captopril; angiotensin converting enzyme inhibitor, on cognitive deficits in the rat hippocampus. Injection of low dose streptozotocin for 4 days resulted in type 1 diabetes. Then, poorly controlled diabetes was mimicked with ineffective daily doses of insulin for 4 weeks. The hyperglycaemia and pancreatic atrophy caused memory disturbance that were identifiable in behavioural tests, hippocampal neurodegeneration, and the following significant changes in the hippocampus, increases in the inflammatory marker interleukin 1β, cholinesterase, the oxidative stress marker malondialdehyde and protein expression of phosphorylated extracellular-signal-regulated kinase and glycogen synthase kinase-3 beta versus decrease in the antioxidant reduced glutathione and protein expression of phosphorylated glycogen synthase kinase-3 beta. Blocking RAS with either drugs along with insulin amended all previously mentioned parameters. Aliskiren stabilized the blood glucose level and restored normal pancreatic integrity and hippocampal malondialdehyde level. Aliskiren showed superior protection against the hippocampal degeneration displayed in the earlier behavioural modification in the passive avoidance test, and the aliskiren group outperformed the control group in the novel object recognition test. We therefore conclude that aliskiren and captopril reversed the diabetic state and cognitive deficits in rats with poorly controlled STZ-induced diabetes through reducing oxidative stress and inflammation and modulating protein expression.

学习和记忆障碍是糖尿病控制不佳的患者随时间发展的明显症状。肾素-血管紧张素系统（RAS）的过度活跃与β细胞功能障碍和糖尿病并发症（包括认知障碍）直接相关。在这里，我们研究了两种RAS修饰剂阿利吉仑的保护作用和分子作用。肾素抑制剂和卡托普利；血管紧张素转换酶抑制剂，对大鼠海马的认知功能障碍。注射低剂量链脲佐菌素4天导致1型糖尿病。然后，将控制不佳的糖尿病模仿为无效胰岛素的每日剂量，持续4周。高血糖和胰腺萎缩会导致记忆障碍，这在行为测试，海马神经变性，以及海马区的以下显着变化，炎症标志物白介素1β，胆碱酯酶，氧化应激标志物丙二醛和磷酸化的细胞外信号调节激酶和糖原合酶激酶-3β的蛋白质表达增加，而抗氧化剂的减少则减少了谷胱甘肽和蛋白的磷酸化糖原合酶激酶3β的表达。用任何一种药物和胰岛素阻断RAS均修正了所有上述参数。阿利吉仑可稳定血糖水平，恢复正常的胰腺完整性和海马丙二醛水平。Aliskiren在被动回避测试中表现出了对早期行为改变所显示的海马变性的优异保护，在新的物体识别测试中，阿利吉仑组的表现优于对照组。因此，我们得出结论，阿利吉仑和卡托普利可以通过降低氧化应激和炎症反应以及调节蛋白表达来逆转STZ诱导的糖尿病控制不佳的大鼠的糖尿病状态和认知缺陷。