阿尔茨海默病(AD),最常见的神经退行性疾病,以行为为特征,认知,和进行性记忆障碍。广泛的神经元损失,不溶性老年性淀粉样β(Aβ)斑块的细胞外积累,细胞内神经原纤维缠结(NFTs)是主要的病理特征。本研究旨在研究多奈哌齐(DON)和己酮可可碱(PTX)联合治疗由CuSO4摄入引起的神经退行性疾病(实验性AD)的实验大鼠的治疗效果。本研究使用30只成年雄性Wistar大鼠(140-160g)。首先通过在饮用水(10mg/L)中补充CuSO4在大鼠中诱导14周的AD。AD组未接受进一步治疗。口服DON(10mg/kg/天),PTX(100mg/kg/天),其他三组的DON+PTX从CuSO4摄入第10周开始,共4周。皮质标志物,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)和海马标记,如β-淀粉样前体蛋白裂解酶1(BACE1),磷酸化Tau(p-tau),Clusterin(CLU),肿瘤坏死因子-α(TNF-α),caspase-9(CAS-9),Bax,测量Bcl-2。通过使用苏木精和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。CuSO4引起不利的组织学和生化改变。在施用DON和PTX后,海马的组织学损伤被抑制。脑组织的AChE水平,MDA,BACE1,p-tau,CLU,CAS-9,Bax,TNF-α显著升高,而脑组织的ACH水平,TAC,与未处理的对照组相比,CuSO4处理的大鼠中Bcl-2显著降低。DON或PTX对大多数研究参数的诱导作用是可比较的。与单独使用DON和PTX的联合治疗相比,效果显着。然而,仍需要更多的临床和临床前研究来进一步确认和证明这种联合用药的长期疗效.
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.