[關(guān)鍵詞]
[摘要]
目的 觀察藏藥佐太的抗抑郁和抗焦慮作用,并探討其可能作用機(jī)制。方法 1)初步評(píng)價(jià)實(shí)驗(yàn):在小鼠ig給予6.07、60.70、303.49、606.97 mg/kg佐太14 d后,通過強(qiáng)迫游泳實(shí)驗(yàn)和開場實(shí)驗(yàn)初步評(píng)價(jià)佐太對(duì)抑郁和焦慮的影響,同時(shí)通過檢測小鼠血清中5-羥色胺(5-HT)和去甲腎上腺素(NE)水平來探討佐太產(chǎn)生影響的可能作用機(jī)制。2)不可預(yù)測性慢性溫和應(yīng)激模型(CUMS)實(shí)驗(yàn):建立CUMS模型,ig給予6.07、60.70、606.97 mg/kg佐太后,通過小鼠體質(zhì)量變化、糖水偏愛實(shí)驗(yàn)、小鼠懸尾實(shí)驗(yàn)、開場實(shí)驗(yàn)和埋珠實(shí)驗(yàn)評(píng)價(jià)佐太對(duì)CUMS模型小鼠的抗抑郁和抗焦慮作用,同時(shí)檢測小鼠血清中皮質(zhì)酮(CORT)、促腎上腺皮質(zhì)激素(ACTH)和下丘腦中促腎上腺皮質(zhì)激素釋放激素(CRH)水平,測定佐太對(duì)CUMS模型小鼠下丘腦-垂體-腎上腺(HPA)軸的影響。結(jié)果 1)佐太能夠顯著減少小鼠強(qiáng)迫游泳實(shí)驗(yàn)中不動(dòng)時(shí)間(6.07、60.70、303.49、606.97 mg/kg);增加小鼠在開場實(shí)驗(yàn)中中央?yún)^(qū)停留時(shí)間百分率(606.97 mg/kg)和中央?yún)^(qū)運(yùn)動(dòng)百分比(303.49、606.97 mg/kg);增加小鼠血清中5-HT(6.07、606.97 mg/kg)和NE(6.07、303.49、606.97 mg/kg)水平。2)CUMS實(shí)驗(yàn)中,與對(duì)照組比較,經(jīng)過42 d CUMS慢性應(yīng)激小鼠表現(xiàn)出明顯的抑郁和焦慮樣行為,包括糖水偏愛率的降低、懸尾不動(dòng)時(shí)間顯著增加、開場實(shí)驗(yàn)中運(yùn)動(dòng)時(shí)間、中央?yún)^(qū)域停留時(shí)間及運(yùn)動(dòng)距離的減少和周邊區(qū)域運(yùn)動(dòng)距離的增加、埋珠實(shí)驗(yàn)中埋珠個(gè)數(shù)的增加。而ig給予佐太(6.07、60.70、606.97 mg/kg)能夠顯著改善CUMS模型引起的上述癥狀,并且佐太(6.07、60.70 mg/kg)能夠顯著降低CORT、ACTH和CRH水平,抑制CUMS模型引起的HPA軸亢進(jìn)。結(jié)論 佐太具有一定的抗抑郁和抗焦慮作用,并且其作用機(jī)制可能與升高5-HT、NE水平和抑制HPA軸亢進(jìn)有關(guān)。
[Key word]
[Abstract]
Objective To evaluate the antidepressant-like and anxiolytic-like effects of Tibetan medicine Zuotai and discuss the possible mechanism. Method 1) Preliminary estimate test: the forced swimming test (FST), open field test (OFT), serum serotonin (5-HT) and norepinephrine (NE) were used to preliminary estimate the antidepressant and anxiolytic effects after ig administration with 6.07, 60.70, 303.49, and 606.97 mg/kg Zuotai. 2) chronic unpredictable mild stress (CUMS): in the CUMS model, mice weight, tail suspension test (TST), OFT, marble burying test were used to analyze the depression and anxiety symptoms. Serum corticosterone (CORT), adrenocorticotrophic hormone (ACTH), and adrenocorticotrophic hormone releasing hormone (CRH) expression in the hypothalamus were also determined to elucidate the neurochemical mechanisms. Result 1) Zuotai at doses of 6.07, 60.70, 303.49, and 606.97 mg/kg significantly reduced the immobility time in the FST, increased the time and distance of center percentage in the OFT and significantly increased the level of serum 5-HT (6.07 and 606.97 mg/kg) and NE (6.07, 303.49, 606.97 mg/kg) in KM mice after 14 d treatment. 2) The experimental results showed that CUMS, being lasted for 42 d, caused depression-like and anxiety-like symptoms in mice, including reduced mice weight changes, significant reduced in sucrose consumption, increased immobility in the tail suspension test, decreased the movement time and the time and distance of center percentage in the OFT, and increased the number of buried marble in marble burying test. Daily KM mice given Zuotai at doses of 6.07, 60.70, and 606.97 mg/kg by ig administration during the 42 d can significantly alleviated the CUMS-induced depression-like and anxiety-like behaviors and decreased the levels of CORT, ACTH, and CRH (6.07 and 60.70 mg/kg). Conclusion The present research indicates that Zuotai possesses potentially antidepressant-like and anxiolytic-like effects, which may be mediated partly through 5-HT, NE, and HPA axis.
[中圖分類號(hào)]
[基金項(xiàng)目]
國家自然科學(xué)基金面上項(xiàng)目(81374063);青海省重點(diǎn)實(shí)驗(yàn)室發(fā)展專項(xiàng)(2014-Z-Y02);中國科學(xué)院“西部之光”重點(diǎn)項(xiàng)目(Y529021211)