海南医科大学学报

目的：探索海南番木瓜提取物对D-半乳糖所致小鼠衰老模型的改善学习记忆障碍和抗衰老的作用。方法：将水迷宫实验筛选认知能力正常的4月龄昆明种小鼠共72只，根据随机平均原则，分为阴性对照组、模型组、吡拉西坦组以及海南番木瓜提取物高、中、低剂量组（400、200、100 mg/kg），共6组，每组12只，海南番木瓜提取物与吡拉西坦组每天以灌胃给药途径给予以上药物，阴性对照与模型两个组以同样的给药途径给予等量0.9%NaCl溶液。各组小鼠每周称重1次；给药的同时，每天用2%D-半乳糖对除阴性对照组小鼠外各组小鼠进行腹腔注射，阴性对照组小鼠注射0.9%NaCl溶液，共7周。49 d后，通过Morris水迷宫观察小鼠的空间学习记忆能力；后取各组小鼠脑组织分别检测其超氧化物歧化酶（Superoxide Dismutase,SOD）、丙二醛（malondialdehyde,MDA）、过氧化氢酶（catalase,CAT）、一氧化氮合酶（Nitric oxide synthase,NOS）的含量；以HE染色法观察海马组织病理学的改变，Western blot测定脑组织核因子-E2-相关因子（Nrf2）蛋白表达水平。结果：海南番木瓜提取物干预衰老模型小鼠后，其高、中、低剂量组可不同程度地缩短小鼠的游泳时间和游泳距离，同时能升高小鼠脑组织SOD、CAT、NOS活力和降低MDA含量；且高剂量组表现最佳，优于吡拉西坦组（P<0.01）；同时能通过减少神经元细胞核固缩来改善小鼠海马组织中神经元组织病理学改变，并能呈剂量依赖性提高小鼠脑组织中Nrf2蛋白的表达。结论：海南番木瓜一定程度上有延缓D-半乳糖所致亚急性衰老小鼠的各项体征，具有一定的抗衰老的作用，其作用可能与Nrf2信号通路有一定的联系。

Objective:To explore the effects of Hainan papaya extract on learning and memory impairment and anti-aging in D-galactose-induced aging mice. Methods:A total of 72 Kunming mice with normal cognitive ability screened by water maze test were randomly divided into negative control group,model group,piracetam group,high,medium and low dose groups of Hainan papaya extract(400 mg/kg,200 mg/kg,100 mg/kg),with 12 mice in each group. Hainan papaya extract and piracetam group were given the above drugs by gavage every day,The negative control and model groups were given the same amount of 0.9% NaCl solution in the same way. Mice in each group were weighed once a week;At the same time,except for the negative control group,mice in each group were intraperitoneally injected with 2% D-galactose every day,and the negative control group was intraperitoneally injected with normal saline for 7 weeks.After 7 weeks,We observed each group of mice's capacity of learning and memory by Morris water maze behavioral test;Then,the content of superoxide dismutase(SOD),malondialdehyde(MDA),catalase(CAT),and nitric oxide synthase(NOS)were measured;On the other hand,we observed the hippocampus' histopathological changes by hematoxylin-eosin staining,and measured the protein expression of nuclear factor-E2-related factor(Nrf2)in brain tissue of mice in each group by Western blot. Results:After the intervention of Hainan papaya extract on aging model mice,the high,medium and low dose groups could shorten the swimming time and swimming distance of mice to varying degrees,increase the activities of SOD,CAT and NOS in mouse brain tissue and reduce the content of MDA,The performance of high dose group was better than piracetam group(P<0.01). At the same time,it can improve the histopathological changes of neurons in mouse hippocampus by reducing neuronal nuclear pyknosis,and increase the expression of Nrf2 protein in mouse brain in a dose-dependent manner. Conclusion:Hainan papaya extract is able to postpone various physical signs of subacute aging mice caused by D-galactose,and possesses definite anti-aging and antioxidant effects,which may be related to the regulation of Nrf2 signal pathway.