Abstract

Deregulation of brain Ca²⁺ homeostasis is linked with oxidative stress, mitochondrial dysfunction, neurodegeneration, loss of synaptic plasticity, and cholinergic deficits. Earlier chronic administration of calcium channel blockers (L-type CCBs) has afforded relief in Alzheimer’s disease (AD) symptoms. Azelnidipine (AZL) is a long duration L-type Ca²⁺ channel blocker recently included in anti-hypertensive therapy. The present study reveals the role of AZL in the management of ICV-STZ induced AD in rats. Wistar rats of either sex (aged 12–15 weeks and weight range 260–280 g) were divided into 6 groups in single blind fashion and stereotaxic surgery was performed. Streptozotocin (3 mg/kg) was injected (ICV) in five groups and one group was administered with ACSF. AZL was administered (1.5, 3 and 6 mg/kg; p.o.) to separate groups of ICV-STZ pre-treated rats for 14 successive days. Memory of rats was measured using elevated plus maze and novel object recognition task. After behavioral evaluation, the animals were sacrificed and whole brains were isolated for estimation of AChE activity, TBARS and GSH levels. ICV-STZ treatment increased the brain AChE activity, TBARS level, decreased GSH level, and thereby impaired the memory of rats. The Ca²⁺ antagonistic property of AZL attenuated the STZ induced derangement of biochemical parameters and resurrected the memory functions in rats. This study exhibited that long-term blockade of the L-type Ca²⁺ channels using azelnidipine mitigates AD type dementia owing to its neuroprotective and antioxidant properties.

中文翻译：

---

Azelnidipine改善链脲佐菌素治疗大鼠的痴呆症：氧化应激和钙之间的相互作用。

摘要

脑Ca ²⁺稳态的失调与氧化应激，线粒体功能障碍，神经变性，突触可塑性丧失和胆碱能缺乏有关。早期长期施用钙通道阻滞剂（L型CCB）可以缓解阿尔茨海默氏病（AD）症状。Azelnidipine（AZL）是长期L型Ca ²⁺通道阻滞剂最近被纳入抗高血压治疗。本研究揭示了AZL在ICV-STZ诱导的大鼠AD管理中的作用。将任意性别（年龄12-15周，体重范围260-280 g）的Wistar大鼠以单盲方式分为6组，并进行立体定向手术。五组注射链脲佐菌素（3 mg / kg）（ICV），一组给予ACSF。服用AZL（1.5、3和6 mg / kg；口服）以连续14天将各组ICV-STZ预处理的大鼠分开。使用高架迷宫和新颖的物体识别任务来测量大鼠的记忆。进行行为评估后，处死动物并分离全脑以评估AChE活性，TBARS和GSH水平。ICV-STZ处理可增加大脑AChE活性，TBARS水平，降低GSH水平，从而损害大鼠的记忆力。AZL的Ca ²⁺拮抗特性减弱了STZ诱导的生化参数紊乱并恢复了大鼠的记忆功能。这项研究表明，使用氮卓尼平长期阻断L型Ca ²⁺通道可减轻AD型痴呆症，因为它具有神经保护和抗氧化特性。