The objective of this study was to evaluate the combined and independent effects of exercise training and L-Arginine loaded chitosan nanoparticles (LA CNPs) supplementation on hippocampal Tau, App, Iba1, and ApoE gene expression, oxidative stress, β-secretase enzyme activity, and hippocampus histopathology in aging rats. Thirty-five male Wistar rats were randomly assigned to five groups (n = 7 in each): Young (8 weeks old), Old (20 months old), old + L-arginine supplementation (Old Sup), old + exercise (Old Exe) and old + L-arginine supplementation + exercise (Old Sup + Exe). LA CNPs were administered to the supplement groups through gavage at a dosage of 500 mg/kg/day for 6-weeks. Exercise groups were subjected to a swimming exercise program five days/week for the same duration. Upon the completion of their interventions, the animals underwent behavioral and open-field task tests and were subsequently sacrificed for hippocampus genetic and histopathological evaluation. For histopathological analysis of brain, Cresyl violet staining was used. Congo Red staining was employed to confirm amyloid plaques in the hippocampus. Expressions of Tau, App, Iba1, and ApoE genes were determined by real-time PCR. In contrast to the Old group, Old Exe and Old Sup + Exe groups spent more time in the central space in the open field task (p < 0.05) and have more live cells in the hippocampus. Old rats (Old, Old Sup and Old Exe groups) exhibited a significant Aβ peptide accumulation and increases in APP, Tau, Iba1, APOE-4 mRNA and MDA, along with decreases in SOD compared to the young group (p < 0.05). However, LA CNPs supplementation, exercise, and their combination (Old Sup, Old Exe and Old Sup + Exe) significantly reduced MDA, Aβ plaque as well as APP, Tau, Iba1, and APOE-4 mRNA compared to the Old group (p < 0.05). Consequently, the administration of LA CNPs supplements and exercise might regulate the risk factors of hippocampus cell and tissue.

本研究的目的是评估运动训练和 L-精氨酸负载壳聚糖纳米颗粒 (LA CNP) 补充剂对海马Tau、App、Iba1和 ApoE 基因表达、氧化应激、β-分泌酶活性、和衰老大鼠海马组织病理学。将 35 只雄性 Wistar 大鼠随机分为 5 组（每组n  = 7）：年轻组（8 周龄）、老年组（20 个月龄）、老年 + L-精氨酸补充组（Old Sup）、老年 + 运动组（Old Exe）和老+L-精氨酸补充+运动（Old Sup + Exe）。LA CNPs 通过管饲方式给予补充剂组，剂量为 500 mg/kg/天，持续 6 周。锻炼组每周进行五天的游泳锻炼计划，持续时间相同。干预完成后，这些动物接受了行为和旷场任务测试，随后被处死以进行海马体遗传和组织病理学评估。对于脑的组织病理学分析，使用甲酚紫染色。采用刚果红染色来确认海马中的淀粉样斑块。通过实时 PCR 测定Tau、App、Iba1和 ApoE 基因的表达。与 Old 组相比，Old Exe 和 Old Sup + Exe 组在旷场任务中在中央空间花费了更多的时间（p  < 0.05），并且海马体中有更多的活细胞。与年轻组相比，老年大鼠（Old、Old Sup 和 Old Exe 组）表现出显着的 Aβ 肽积累，APP、Tau、Iba1、APOE-4 mRNA 和 MDA增加，同时 SOD 下降（ p  < 0.05）。然而，与 Old 组相比，LA CNP 补充、锻炼及其组合（Old Sup、Old Exe 和 Old Sup + Exe）显着减少了 MDA、Aβ 斑块以及APP、Tau、Iba1 和 APOE-4 mRNA（ p  < 0.05）。因此，服用 LA CNP 补充剂和运动可能会调节海马细胞和组织的危险因素。