目的: 探讨锁阳黄酮(cynomorium songaricum flavonoids, CSF)对快速老化小鼠(senescence-accelerated mice prone 8, SAMP8)认知功能障碍的影响及其作用机制。方法: 选取30只7月龄雄性SAMP8小鼠,随机分为对照组、锁阳黄酮组、多奈哌齐组。锁阳黄酮组给予锁阳黄酮50 mg/(kg·d)连续灌胃20 d,多奈哌齐组给予多奈哌齐0.71 mg/(kg·d)灌胃20 d。给药结束后采用Morris水迷宫评价认知功能表现,尼氏染色观察海马锥体细胞形态并计数;蛋白免疫印迹测定海马区醌氧化还原酶(NADPH:quinone oxidoreductase-1, NOQ1)、核因子E2相关因子2(nuclear factor e2 related factor 2, Nrf2)、Kelch环氧氯丙烷相关蛋白1(Kelch-like ECH-associated protein 1, Keap1)蛋白表达水平;酶联免疫吸附实验(Enzyme-linked immunosorbent assay, ELISA)测定血清谷胱甘肽过氧化物酶(glutathione peroxidase, GSH-Px)和超氧化物歧化酶(superoxide dismutase, SOD)活性、丙二醛(malondialdehyde, MDA)的含量。结果: 与对照组相比,锁阳黄酮组小鼠上台前路程和逃避潜伏期减小,穿越平台次数与目标象限时间百分比增加(P＜0.05);与对照组相比,锁阳黄酮组、多奈哌齐组小鼠海马区Nrf2、Keap1、NOQ1蛋白表达量升高(P＜0.05);与对照组相比,锁阳黄酮组小鼠血清SOD和GSH-Px的活性增高(P＜0.05),MDA含量降低(P＜0.05)。结论: 锁阳黄酮能改善SAMP8小鼠认知功能障碍,其机制可能与调控Nrf2-Keap1通路抑制氧化应激相关。
Objective: To explore the effect and mechanism of cynomorium songaricum flavonoids (CSF) on senescence-accelerated mice prone 8 (SAMP8). Methods: Thirty 7-month-old male SAMP8 mice were selected and randomly divided into control group, cynomorium songaricum flavonoids group, and donepezil group. The SAMP8 mice in the cynomorium songaricum flavonoids group were given cynomorium songaricum flavonoids 50 mg/(kg·d) by gavage for 20 days, and the donepezil group was given donepezil 0.71 mg/(kg·d) by gavage for 20 days. After administration, the Morris water maze was used to evaluate the cognitive function, and Nissl staining was used to observe the morphology and count of hippocampal pyramidal cells. The protein expression levels of NADPH: quinone oxidoreductase-1 (NOQ1), nuclear factor e2 related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) in hippocampus were determined by Western blotting. The activity of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD) and the content of malondialdehyde(MDA) in serum were measured by ELISA. Results: Compared with the control group, the distance and escape latency of the mice in the cynomorium songaricum flavonoids were decreased, and the percentage of the number of crossing the platform and the time of the target quadrant were increased (P＜0.05). Compared with the control group, the expression of Nrf2, Keap1 and NOQ1 protein in the hippocampus of the mice in the cynomorium songaricum flavonoids group and donepezil group was increased (P＜0.05). Compared with the control group, the activity of SOD and GSH-Px in the serum of mice in the cynomorium songaricum flavonoids group was increased (P＜0.05), and the content of MDA was decreased (P＜0.05). Conclusion: Cynomorium songaricum flavonoids can improve cognitive dysfunction in SAMP8 mice, and its mechanism may be related to regulating the Nrf2 Keap1 pathway to inhibit oxidative stress.
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