目的 探究番茄紅素調(diào)控Kelch樣環(huán)氧氯丙烷相關(guān)蛋白1（Keap1）/核因子E2相關(guān)因子2（Nrf2）/抗氧化反應(yīng)元件（ARE）通路，影響精神分裂癥大鼠的氧化應(yīng)激反應(yīng)和認(rèn)知功能。方法 構(gòu)建精神分裂癥大鼠模型，將大鼠隨機(jī)分為對(duì)照組、氯丙嗪組、模型組以及番茄紅素高、低劑量組和番茄紅素+Nrf2抑制劑組，每組各10例。Morris水迷宮實(shí)驗(yàn)檢測(cè)各組大鼠認(rèn)知功能；Tunel染色觀察并計(jì)算各組大鼠海馬組織中神經(jīng)元凋亡率；酶聯(lián)免疫吸附測(cè)定法（ELISA）檢測(cè)大鼠血清中過氧化氫酶（CAT）、谷胱甘肽過氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）水平；Western blotting法檢測(cè)各組大鼠海馬組織中Keap1、Nrf2和ARE下游抗氧化蛋白HO-1的表達(dá)水平。結(jié)果 與模型組相比，番茄紅素組大鼠水迷宮實(shí)驗(yàn)中逃避潛伏期明顯縮短（2～5d），海馬組織細(xì)胞凋亡率顯著降低，血清CAT、GSH-Px、SOD水平和海馬組織Keap1、Nrf2、HO-1蛋白表達(dá)量顯著升高（P<0.05）；與番茄紅素高劑量組相比，番茄紅素低劑量組、番茄紅素+Nrf2抑制劑組大鼠水迷宮實(shí)驗(yàn)中逃避潛伏期明顯延長(zhǎng)（2～5d），海馬組織細(xì)胞凋亡率顯著升高，血清CAT、GSH-Px、SOD水平和海馬組織Keap1、Nrf2、HO-1蛋白表達(dá)量顯著降低（P<0.05）。結(jié)論 番茄紅素可通過調(diào)控Keap1/Nrf2/ARE通路，促進(jìn)Keap1、Nrf2、HO-1的表達(dá)，緩解氧化應(yīng)激，改善認(rèn)知功能，從而緩解精神分裂，改善病情。

Objective To explore lycopene participates in the oxidative stress response and cognitive function of schizophrenia rats by regulating Kelch-like epichlorohydrin-related protein 1 (Keap1)/nuclear factor erythroid-2 related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. Methods A schizophrenia rat model was constructed, and the rats were randomly divided into control group, chlorpromazine group, model group, high-dose lycopene group, low-dose lycopene group, and lycopene combined with Nrf2 inhibition group, and there were 10 cases in each group. Morris water maze test was performed to detect the cognitive function of rats in each group. Tunel staining was performed to observe and calculate the apoptosis rate of neurons in the hippocampus of rats in each group. The enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of serum catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) of rats. Western blotting methods were performed to measure the expression levels of Keap1, Nrf2, and ARE downstream antioxidant protein HO-1 in the hippocampus of rats in each group. Results Compared with the model group, the escape latency in the water maze test of the lycopene groups was significantly shortened (2 — 5 d), the apoptosis rate of hippocampal cells was significantly decreased, the serum CAT, GSH-Px, SOD contents and hippocampal tissue Keap1, Nrf2, HO-1 protein expression were significantly increased (P < 0.05). Compared with the high-dose lycopene group, the low-dose lycopene group and the lycopene combined with Nrf2 inhibition group had significantly longer escape latency (2 — 5 d) in the water maze test, the apoptosis rate of hippocampal cells was significantly increased, the serum CAT, GSH-Px, and SOD contents and hippocampal tissue Keap1, Nrf2, HO-1 protein expression were significantly decreased (P < 0.05). Conclusion Lycopene can regulate the Keap1/Nrf2/ARE pathway, promote the expression of Keap1, Nrf2, and HO-1, relieve oxidative stress and ameliorate cognitive function, thereby relieving schizophrenia and improving the disease.

R965

河南省醫(yī)學(xué)科技攻關(guān)計(jì)劃項(xiàng)目（2017T04021）