Alhowail Ahmad, Aldawsari Mohammed F, Aldubayan Maha
Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah, 51452, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj, 11942, Saudi Arabia.
Drug Des Devel Ther. 2025 Jul 31;19:6605-6618. doi: 10.2147/DDDT.S525690. eCollection 2025.
Type 2 diabetes mellitus (T2DM) is a widespread metabolic illness that compromises cognitive function by inducing inflammation and oxidative damage. Diabetes mellitus is treated with many types of medications, including tirzepatide (TZP) and pioglitazone (PIO), which have also been shown to enhance cognitive deficits associated with the condition. This study intends to investigate the neuroprotective effects of TZP and PIO on type 2 diabetic mellitus (T2DM) via mitigating neuroinflammation and oxidative stress, along with enhancing cognitive impairment in rats as models with T2DM.
A total of six distinct groups of sixty albino rat males (n = 10) were allocated at random: Saline, TZP, PIO, T2DM, T2DM+TZP, and T2DM+PIO. Intramuscular doses of streptozotocin (50 mg/kg) and nicotinamide (120 mg/kg) precipitated T2DM. The TZP and PIO therapies persisted for a duration of 15 days. The survival percentage, body weight, behavioral assessments (Y-maze, novel object recognition (NOR)), glucose concentrations, inflammatory mediators tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin-1 beta (IL-1β), as well as oxidative stress biomarkers superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), and lipid peroxidation were evaluated following the conclusion of the treatments.
The results demonstrate that diabetes decreased survival rates, body weight, cognitive function, increased glucose levels, neuroinflammation, and oxidative stress. The TZP and PIO increased survival rates and cognitive function as well as decreased glucose levels, neuroinflammation, and oxidative stress in diabetic rats, with PIO demonstrating a more pronounced effect on neuroinflammation and oxidative stress, contrasted with TZP.
This study concluded that TZP and PIO enhanced cognitive impairment in diabetic rats, with PIO demonstrating superior efficacy in contrast to TZP.
2型糖尿病（T2DM）是一种广泛存在的代谢性疾病，通过引发炎症和氧化损伤损害认知功能。糖尿病采用多种药物治疗，包括替尔泊肽（TZP）和吡格列酮（PIO），研究表明这些药物也会加重与该病症相关的认知缺陷。本研究旨在通过减轻神经炎症和氧化应激，以及改善作为T2DM模型的大鼠的认知障碍，来研究TZP和PIO对2型糖尿病（T2DM）的神经保护作用。
将总共六组每组十只的六十只雄性白化大鼠随机分组：生理盐水组、TZP组、PIO组、T2DM组、T2DM + TZP组和T2DM + PIO组。通过肌肉注射链脲佐菌素（50 mg/kg）和烟酰胺（120 mg/kg）诱发T2DM。TZP和PIO治疗持续15天。治疗结束后，评估存活率、体重、行为评估（Y迷宫、新物体识别（NOR））、血糖浓度、炎症介质肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）和白细胞介素-（IL-1β），以及氧化应激生物标志物超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）、丙二醛（MDA）和脂质过氧化。
结果表明，糖尿病降低了存活率、体重、认知功能，增加了血糖水平、神经炎症和氧化应激。TZP和PIO提高了糖尿病大鼠的存活率和认知功能，降低了血糖水平、神经炎症和氧化应激，与TZP相比，PIO对神经炎症和氧化应激的影响更为显著。
本研究得出结论，TZP和PIO改善了糖尿病大鼠的认知障碍，与TZP相比，PIO显示出更好的疗效。
