Alzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by behavioral, cognitive, and progressive memory impairments. Extensive neuronal loss, extracellular accumulation of insoluble senile amyloid-β (Aβ) plaques, and intracellular neurofibrillary tangles (NFTs) are the major pathological features. The present study aimed to investigate the therapeutic effect of donepezil (DON) and pentoxifylline (PTX) in combination to combat the neurodegenerative disorders (experimental AD) induced by CuSO₄ intake in experimental rats. Thirty adult male Wistar rats (140–160 g) were used in this study. AD was first induced in rats by CuSO₄ supplement to drinking water (10 mg/L) for 14 weeks. The AD group received no further treatment. Oral treatment with DON (10 mg/kg/day), PTX (100 mg/kg/day), or DON + PTX for the other three groups was started from the 10th week of CuSO₄ intake for 4 weeks. Cortex markers like acetylcholine (ACh), acetylcholinesterase (AChE), total antioxidant capacity (TAC), and malondialdehyde (MDA) and hippocampus markers like β-amyloid precursor protein cleaving enzyme 1 (BACE1), phosphorylated Tau (p-tau), Clusterin (CLU), tumor necrosis factor-α (TNF-α), caspase-9 (CAS-9), Bax, and Bcl-2 were measured. The histopathology studies were done by using hematoxylin and eosin and Congo red stains as well as immunohistochemistry for neurofilament. CuSO₄ induced adverse histological and biochemical changes. The histological injury in the hippocampus was inhibited following the administration of the DON and PTX. The brain tissue levels of AChE, MDA, BACE1, p-tau, CLU, CAS-9, Bax, and TNF-α were significantly increased, while brain tissue levels of ACh, TAC, and Bcl-2 were significantly decreased in CuSO₄-treated rats as compared with the untreated control group. The effects induced by either DON or PTX on most studied parameters were comparable. Combined treatment of DON and PTX induced remarkable results compared with their individual use. However, more clinical and preclinical studies are still required to further confirm and prove the long-term efficacy of such combination.

阿尔茨海默病 (AD) 是最常见的神经退行性疾病，其特征是行为、认知和进行性记忆障碍。广泛的神经元丢失、不溶性老年淀粉样蛋白-β（Aβ）斑块在细胞外积聚以及细胞内神经原纤维缠结（NFT）是主要的病理特征。本研究旨在探讨多奈哌齐 (DON) 和己酮可可碱 (PTX) 联合治疗实验大鼠因摄入 CuSO ₄引起的神经退行性疾病（实验性 AD）的治疗效果。本研究使用了 30 只成年雄性 Wistar 大鼠（140-160 克）。首先通过在饮用水中添加CuSO ₄ (10 mg/L) 14 周来诱导大鼠 AD 。AD组没有接受进一步的治疗。_{其他三组从摄入CuSO 4}第10周开始口服DON(10mg/kg/天)、PTX(100mg/kg/天)或DON+PTX治疗，持续4周。皮质标记物，如乙酰胆碱 (ACh)、乙酰胆碱酯酶 (AChE)、总抗氧化能力 (TAC) 和丙二醛 (MDA)，以及海马标记物，如 β-淀粉样蛋白前体蛋白裂解酶 1 (BACE1)、磷酸化 Tau (p-tau)、簇蛋白测量了 (CLU)、肿瘤坏死因子-α (TNF-α)、caspase-9 (CAS-9)、Bax 和 Bcl-2。通过使用苏木精、曙红和刚果红染色以及神经丝的免疫组织化学进行组织病理学研究。CuSO ₄引起不利的组织学和生化变化。施用 DON 和 PTX 后，海马组织学损伤受到抑制。_{CuSO 4}处理后脑组织AChE、MDA、BACE1、p-tau、CLU、CAS-9、Bax、TNF-α水平显着升高，而ACh、TAC、Bcl-2水平显着降低-治疗的大鼠与未治疗的对照组相比。DON 或 PTX 对大多数研究参数的影响是相当的。与单独使用相比，DON 和 PTX 联合治疗效果显着。但仍需要更多的临床和临床前研究来进一步证实和证明这种组合的长期疗效。