【摘要】： 目的通過觀察有氧運動對慢性輕度不可預期性應激(chronic unpredictedmild stress,CUMS)大鼠曠場行為、急應激暴露時血清皮質(zhì)醇、白細胞介素-1β、海馬與前額葉皮層熱休克蛋白70和誘導型一氧化氮合酶表達的影響,探討非藥物性應對策略有氧運動對應激性神經(jīng)、內(nèi)分泌和免疫指標的影響。方法32只成年雄性Wistar大鼠隨機分為對照組、CUMS組、拉貝洛爾組、有氧運動組,每組8只。CUMS組、拉貝洛爾組、有氧運動組采用21天慢性輕度不可預期性應激造模,造模過程中拉貝洛爾組大鼠在每次應激刺激前30min接受拉貝洛爾(30mg/kg)灌胃,有氧運動組大鼠進行無負重遞增中等強度有氧游泳運動。所有動物在實驗組造模結束后采用足底電擊(1.5mA,電擊5s休息55s,共60次)進行急應激暴露。以曠場實驗評價大鼠行為學改變;以放射免疫法測定血清皮質(zhì)醇和白細胞介素-1β含量;以免疫組織化學染色定位海馬與前額葉皮層熱休克蛋白70表達,蛋白免疫印跡法檢測海馬與前額葉皮層熱休克蛋白70和誘導型一氧化氮合酶的表達。結果(1)與對照組相比,CUMS組大鼠中央格停留時間延長(P＜0.05),水平運動和垂直運動得分降低(P＜0.01;P＜0.01),清潔次數(shù)減少(P＜0.05);拉貝洛爾組中央格停留時間延長(P＜0.05),垂直運動得分降低(P＜0.01),清潔次數(shù)減少(P＜0.05),水平運動得分改善無統(tǒng)計學意義;有氧運動組各指標與對照組相比無顯著性差異。與CUMS組比較,有氧運動組中央格停留時間縮短(P＜0.01),水平運動得分與垂直運動得分增加(P＜0.01;P＜0.01),清潔次數(shù)增加(P＜0.05)。拉貝洛爾組與有氧運動組相比中央格停留時間延長(P＜0.05),垂直運動得分降低(P＜0.01),清潔次數(shù)減少(P＜0.05)。(2)有氧運動組大鼠血清皮質(zhì)醇含量較CUMS組、拉貝洛爾組升高,差異有統(tǒng)計學意義(P＜0.05;P＜0.05)。各組大鼠血清白細胞介素-1β水平均無統(tǒng)計學差異。(3)與CUMS模型組比,拉貝洛爾組前額葉皮層熱休克蛋白70水平顯著升高(P＜0.05),有氧運動組海馬與前額葉皮層熱休克蛋白70水平均顯著升高(P＜0.01;P＜0.05)。且有氧運動組海馬熱休克蛋白70水平顯著高于拉貝洛爾組(P＜0.05)。(4)CUMS組大鼠海馬組織中誘導型一氧化氮合酶表達顯著高于對照組(P＜0.01);與CUMS組相比,拉貝洛爾組海馬與前額葉皮層誘導型一氧化氮合酶表達均顯著降低(P＜0.05;P＜0.05);有氧運動組各腦區(qū)誘導型一氧化氮合酶表達水平與對照組比較無顯著差異,但均顯著低于CUMS組(P＜0.01;P＜0.01)。結論(1)CUMS可導致大鼠產(chǎn)生抑郁性行為,加重海馬與前額葉皮層細胞應激損傷。(2)有氧運動可顯著改善慢性輕度不可預期性應激大鼠行為學指標,穩(wěn)定急應激暴露時下丘腦-垂體-腎上腺皮質(zhì)軸的功能,通過顯著增加海馬與前額葉皮層熱休克蛋白70表達、降低誘導型一氧化氮合酶表達增強機體應激抵抗力。(3)非選擇性腎上腺素能受體拮抗劑拉貝洛爾可部分改善慢性輕度不可預期性應激大鼠行為學指標,對海馬與前額葉皮層均有一定程度的保護作用。
[Abstract]:Objective To investigate the effects of aerobic exercise on open field behavior, serum cortisol, interleukin-1 beta, heat shock protein 70 (HSP70) and inducible nitric oxide synthase (INNOS) expression in the hippocampus and prefrontal cortex of chronic unpredictable mild stress (CUMS) rats, and explore the non-drug coping strategies of aerobic exercise. Methods Thirty-two adult male Wistar rats were randomly divided into control group, CUMS group, labetalol group and aerobic exercise group, with 8 rats in each group. Rats in the aerobic exercise group were given moderate-intensity aerobic swimming without increasing load 30 minutes before the second stress stimulation. All the rats in the experimental group were exposed to acute stress by plantar electric shock (1.5mA, 5 s rest for 55 seconds, 60 times). The levels of serum cortisol and interleukin-1 beta were determined by epidemic method, the expression of heat shock protein 70 in hippocampus and prefrontal cortex was localized by immunohistochemical staining, and the expression of heat shock protein 70 and inducible nitric oxide synthase in hippocampus and prefrontal cortex were detected by Western blotting. Results (1) Compared with the control group, the rats in CUMS group were treated with central gating. The retention time was prolonged (P < 0.05), the scores of horizontal and vertical movement were decreased (P < 0.01; P < 0.01), the cleaning times were decreased (P < 0.05), the stay time of central grid was prolonged (P < 0.05), the score of vertical movement was decreased (P < 0.01), the cleaning times were decreased (P < 0.05), and the scores of horizontal movement were not significantly improved in aerobic exercise group. Compared with the control group, the staying time of the central grid was shortened (P < 0.01), the scores of horizontal and vertical movement were increased (P < 0.01, P < 0.01), and the cleaning times were increased (P < 0.05) in the aerobic exercise group. The levels of serum cortisol in aerobic exercise group were significantly higher than those in CUMS group and Labellol group (P < 0.05; P < 0.05). There was no significant difference in the levels of serum interleukin-1 beta in each group. (3) Compared with CUMS model group, the levels of heat shock protein 7 in prefrontal cortex in Labellol group were significantly higher than those in CUMS group and Labellol group (P < 0.05; P < 0.05). The level of HSP70 in hippocampus and prefrontal cortex of aerobic exercise group was significantly higher than that of labetalol group (P < 0.05). (4) The expression of inducible nitric oxide synthase in hippocampus of CUMS group was significantly higher than that of control group (P Compared with CUMS group, the expression of inducible nitric oxide synthase in hippocampus and prefrontal cortex of labetalol group decreased significantly (P (2) Aerobic exercise can significantly improve the behavioral indexes of Chronic Mild Unpredictable Stress rats, stabilize the function of hypothalamus-pituitary-adrenal cortex axis during acute stress exposure, and increase the expression of heat shock protein 70 in hippocampus and prefrontal cortex. (3) Non-selective adrenergic receptor antagonist labetalol can partly improve the behavioral parameters of Chronic Mild Unpredictable Stress Rats and protect the hippocampus and prefrontal cortex to a certain extent.
【學位授予單位】：山東大學
【學位級別】：碩士
【學位授予年份】：2009
【分類號】：R363

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