摘要
目的观察藏药佐太的抗抑郁和抗焦虑作用,并探讨其可能作用机制。方法 1)初步评价实验:在小鼠ig给予6.07、60.70、303.49、606.97 mg/kg佐太14 d后,通过强迫游泳实验和开场实验初步评价佐太对抑郁和焦虑的影响,同时通过检测小鼠血清中5-羟色胺(5-HT)和去甲肾上腺素(NE)水平来探讨佐太产生影响的可能作用机制。2)不可预测性慢性温和应激模型(CUMS)实验:建立CUMS模型,ig给予6.07、60.70、606.97 mg/kg佐太后,通过小鼠体质量变化、糖水偏爱实验、小鼠悬尾实验、开场实验和埋珠实验评价佐太对CUMS模型小鼠的抗抑郁和抗焦虑作用,同时检测小鼠血清中皮质酮(CORT)、促肾上腺皮质激素(ACTH)和下丘脑中促肾上腺皮质激素释放激素(CRH)水平,测定佐太对CUMS模型小鼠下丘脑-垂体-肾上腺(HPA)轴的影响。结果 1)佐太能够显著减少小鼠强迫游泳实验中不动时间(6.07、60.70、303.49、606.97 mg/kg);增加小鼠在开场实验中中央区停留时间百分率(606.97 mg/kg)和中央区运动百分比(303.49、606.97mg/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实验中,与对照组比较,经过42 d CUMS慢性应激小鼠表现出明显的抑郁和焦虑样行为,包括糖水偏爱率的降低、悬尾不动时间显著增加、开场实验中运动时间、中央区域停留时间及运动距离的减少和周边区域运动距离的增加、埋珠实验中埋珠个数的增加。而ig给予佐太(6.07、60.70、606.97 mg/kg)能够显著改善CUMS模型引起的上述症状,并且佐太(6.07、60.70 mg/kg)能够显著降低CORT、ACTH和CRH水平,抑制CUMS模型引起的HPA轴亢进。结论佐太具有一定的抗抑郁和抗焦虑作用,并且其作用机制可能与升高5-HT、NE水平和抑制HPA轴亢进有关。
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 anxiolyfic 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 miee, 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.
出处
《药物评价研究》
CAS
2016年第4期522-530,共9页
Drug Evaluation Research
基金
国家自然科学基金面上项目(81374063)
青海省重点实验室发展专项(2014-Z-Y02)
中国科学院"西部之光"重点项目(Y529021211)
