雪抑乐乳剂对抑郁模型动物行为及脑内单胺类神经递质的影响
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摘要
目的:研究雪抑乐乳剂对抑郁大鼠及小鼠行为的影响,并通过检测抑郁大鼠脑组织单胺类神经递质含量,初步探讨雪抑乐乳剂的抗抑郁作用机理。方法:1、实验动物分组、饲养及给药:筛选Open-Field评分相近的成年SD大鼠及健康昆明种小鼠各70只,按完全数字随机法分为正常对照组(NS),氟西汀(百忧解)阳性对照组,阴性对照组,抑郁模型组,雪抑乐乳剂高、中、低剂量组,每组10只。除正常对照组每笼3～7只外,其余各组分笼饲养,除氟西汀阳性对照组灌胃给药外,其余均采用经鼻粘膜给药方式。2、大鼠抑郁模型制备:除正常组对照组外,其余各组采用慢性不可预知性应激结合孤养制备抑郁大鼠模型,即将10种不同的应激因子(昼夜颠倒、冰水游泳、热应激、摇晃、夹尾、禁水、禁食、倾斜45度湿笼、陌生异常物品和悬尾)在实验全程中随机刺激大鼠21d。3、观察及检测指标:采用小鼠悬尾及大鼠、小鼠强迫游泳实验观察小鼠和大鼠的不动时间及行为变化;计算动物24h饮用1%蔗糖溶液的量,观察动物的奖赏程度;分离大脑、制备脑组织匀浆,荧光分光光度法测定大鼠脑内单胺类神经递质〔去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)和5-羟吲哚乙酸(5-HIAA)〕的含量。结果:1、雪抑乐乳剂低、中、高剂量组和盐酸氟西汀组均有抑制正常小鼠自主活动的作用趋势,但无统计学意义(P>0.05)。2、雪抑乐乳剂中剂量、高剂量能显著缩短小鼠的不动时间。与模型对照组比较均有显著性(P<0.01)。盐酸氟西汀,雪抑乐低剂量组亦明显缩短了小鼠悬尾的不动时间,与模型对照组比较有统计学意义(P<0.05)。与阳性药物盐酸氟西汀比较,雪抑乐高、中、低剂量组差异均无显著性(P>0.05)。3、雪抑乐低、中、高剂量能显著缩短小鼠和大鼠强迫游泳不动时间(P<0.05, P<0.01)。盐酸氟西汀亦缩短了小鼠和大鼠的不动时间(P<0.01)。与正常对照组相比,抑郁症模型组大鼠强迫游泳不动时间显著延长(P<0.01),阴性对照组大鼠强迫游泳不动时间亦显著延长(P<0.05)。与阳性药物盐酸氟西汀比较,雪抑乐乳剂高、中、低各剂量组的作用效果差异无显著性(P>0.05)。4、雪抑乐乳剂高、中、低各剂量组可以改善大鼠的体重下降和增加模型组大鼠的糖水消耗量。5、与正常对照组比较,模型组大鼠脑内NE、DA、5-HT、5-HIAA的含量均明显降低(P<0.01),雪抑乐乳剂各剂量和盐酸氟西汀可明显升高中枢中NE、5-HT、5-HIAA的含量(P=0.000<0.01),雪抑乐乳剂高剂量和氟西汀组DA的含量有升高趋势,差异显著(P=0.033<0.05)。结论:1、小鼠悬尾和强迫游泳实验是筛选雪抑乐抗抑郁作用的较好的实验方法,雪抑乐乳剂可以缩短不动状态时间,又能减少或至少是不影响小鼠的自主活动,雪抑乐乳剂对“行为绝望”动物模型有明显抗抑郁作用。2、慢性不可预见性应激动物模型为较理想的抑郁动物模型,雪抑乐乳剂能明显改善抑郁动物模型的行为学指标,对实验性抑郁动物模型有一定的治疗和预防作用。3、雪抑乐乳剂能明显升高脑内单胺类神经递质如NE、5-HT和5-HIAA的含量,可能是其抗抑郁作用的机理之一。
Objective: To investigate the effect of XueYiLe emulsion on the behaviors of depressed animal and detect the amount of monoamine neurotransmitte in brain of rats. To approach preliminary the antidepressant mechanism of action of XueYiLe emulsion. Methods: 1. Grouping, rearing and administration of experimental animal: To divide randomly adult Sprague-Dawley (SD) rats and 70 healthy KM mice into 7 groups, the normal control group (NS), the depression model, the positive group (Fluoxetine), negative group, XueYiLe emulsion in low, medium, high dosage, there were 10 mice in each group. All mice except the normal control group were single housed. 3～7 mice were breed in a cage for normal control group. All mice or rats were administered medicine by way of mucous membrane of nose expect the intragastric administration for Fluoxetine group. The antidepressant effects of XueYiLe emulsion were observed by the immobile time of the mice in the tail suspension test and the forced swimming test. 2. Preparation of the rat depression model: Isolated-living condition and chronic mild unpredictable stress with being bred in a single cage are applied successively to set up the rat depression model except normal control group, that it is using ten different stressors (the reverse of day and night, the swimming in ice water, heat stress, shaking, clamping the tail, the prohibition against water, abrosia, making the cage humid and a 45-degree angle, strange abnormal thing and tail suspension) at random rats were stimulated during 21 days of experiment. 3. Index of observation and detection: The researcher observed the immobile time to the tail suspension of the mice and the forced swimming of the mice and the rats and behavioral change; Calculated 1% of the sugar solution consumption and observed the extent to reward; The researcher segregated brain, prepared tissue homogenate and determined the amount of the monoamine neurotransmitter (NE, DA, 5-HT, 5-HIAA) in the cerebrum organization through the method of fluorescence. Results: 1. It had the tendency to inhibition the normal mice in autonomic activities by the XueYiLe emulsion in low, medium, high dosage and the Fluoxetine hydrochloride, but it was not statistically significant (P>0.05). 2. It could shorten the immobile time of the mice significantly by XueYiLe emulsion in medium, high dosage, which was significant compared to model and control group (P<0.01). It were also decrease the immobile time of the mice to the tail suspension obviously by XueYiLe emulsion in low dosage and the Fluoxetine hydrochloride, which was significant difference to model and control group (P < 0.05). It was not significant difference between the Fluoxetine hydrochloride and the group of XueYiLe emulsion in low, medium, high dosage (P>0.05). 3. It could shorten the time of the mice and the rats inactivity to the forced swimming significantly by XueYiLe emulsion in low, medium, high dosage (P<0.05, P<0.01). It were also decrease the time of the mice and the rats inactivity to the forced swimming obviously by the Fluoxetine hydrochloride (P<0.01). Compared with the normal control group, it could extend the time of the rats inactivity to the forced swimming significantly in animal depression model (P<0.01). It were also extend the immobile time of the rats to the forced swimming obviously in the negative control group (P<0.05). It was not significant difference between the Fluoxetine hydrochloride and the group of XueYiLe emulsion in low, medium, high dosage (P>0.05). 4. XueYiLe emulsion in low, medium, high dosage could improve the rat weight and increase the sugar consumption in model rats. 5. Compared with the normal control group, the level of NE, DA, 5-HT and 5-HIAA decreased obviously in the rat brain center of the model group (P<0.01). XueYiLe emulsion in low, medium, high dosage and Fluoxetine hydrochloride can increase obviously the level of NE, 5-HT and 5-HIAA (P=0.000<0.01). It had the tendency to increase the level of DA in XueYiLe emulsion in high dosage and Fluoxetine hydrochloride (P=0.033<0.05). The difference has significance. Conclusion: 1. It was a better experimental method to study the anti-depressive action of XueYiLe to the tail suspension and the forced swimming in mice. XueYiLe emulsion had significant anti-depressive for animal depression model in behavioral hopeless, because it can shorten the immobile time of the mice and decrease or at least not affect the autonomic activities of the mice. 2. Chronic unpredictable mild stress and isolated-living model is an ideal animal depression model. The XueYiLe emulsion can improve obviously behavioral index and show curative and preventative effect to the animal depression model. 3. XueYiLe emulsion can increase obviously the amount of monoamine neurotransmitter (NE, 5-HT, 5-HIAA) in the animal depression model, which may be one of the mechanisms of its anti-depressive action.
Objective: To investigate the effect of XueYiLe emulsion on the behaviors of depressed animal and detect the amount of monoamine neurotransmitte in brain of rats. To approach preliminary the antidepressant mechanism of action of XueYiLe emulsion. Methods: 1. Grouping, rearing and administration of experimental animal: To divide randomly adult Sprague-Dawley (SD) rats and 70 healthy KM mice into 7 groups, the normal control group (NS), the depression model, the positive group (Fluoxetine), negative group, XueYiLe emulsion in low, medium, high dosage, there were 10 mice in each group. All mice except the normal control group were single housed. 3～7 mice were breed in a cage for normal control group. All mice or rats were administered medicine by way of mucous membrane of nose expect the intragastric administration for Fluoxetine group. The antidepressant effects of XueYiLe emulsion were observed by the immobile time of the mice in the tail suspension test and the forced swimming test. 2. Preparation of the rat depression model: Isolated-living condition and chronic mild unpredictable stress with being bred in a single cage are applied successively to set up the rat depression model except normal control group, that it is using ten different stressors (the reverse of day and night, the swimming in ice water, heat stress, shaking, clamping the tail, the prohibition against water, abrosia, making the cage humid and a 45-degree angle, strange abnormal thing and tail suspension) at random rats were stimulated during 21 days of experiment. 3. Index of observation and detection: The researcher observed the immobile time to the tail suspension of the mice and the forced swimming of the mice and the rats and behavioral change; Calculated 1% of the sugar solution consumption and observed the extent to reward; The researcher segregated brain, prepared tissue homogenate and determined the amount of the monoamine neurotransmitter (NE, DA, 5-HT, 5-HIAA) in the cerebrum organization through the method of fluorescence. Results: 1. It had the tendency to inhibition the normal mice in autonomic activities by the XueYiLe emulsion in low, medium, high dosage and the Fluoxetine hydrochloride, but it was not statistically significant (P>0.05). 2. It could shorten the immobile time of the mice significantly by XueYiLe emulsion in medium, high dosage, which was significant compared to model and control group (P<0.01). It were also decrease the immobile time of the mice to the tail suspension obviously by XueYiLe emulsion in low dosage and the Fluoxetine hydrochloride, which was significant difference to model and control group (P < 0.05). It was not significant difference between the Fluoxetine hydrochloride and the group of XueYiLe emulsion in low, medium, high dosage (P>0.05). 3. It could shorten the time of the mice and the rats inactivity to the forced swimming significantly by XueYiLe emulsion in low, medium, high dosage (P<0.05, P<0.01). It were also decrease the time of the mice and the rats inactivity to the forced swimming obviously by the Fluoxetine hydrochloride (P<0.01). Compared with the normal control group, it could extend the time of the rats inactivity to the forced swimming significantly in animal depression model (P<0.01). It were also extend the immobile time of the rats to the forced swimming obviously in the negative control group (P<0.05). It was not significant difference between the Fluoxetine hydrochloride and the group of XueYiLe emulsion in low, medium, high dosage (P>0.05). 4. XueYiLe emulsion in low, medium, high dosage could improve the rat weight and increase the sugar consumption in model rats. 5. Compared with the normal control group, the level of NE, DA, 5-HT and 5-HIAA decreased obviously in the rat brain center of the model group (P<0.01). XueYiLe emulsion in low, medium, high dosage and Fluoxetine hydrochloride can increase obviously the level of NE, 5-HT and 5-HIAA (P=0.000<0.01). It had the tendency to increase the level of DA in XueYiLe emulsion in high dosage and Fluoxetine hydrochloride (P=0.033<0.05). The difference has significance. Conclusion: 1. It was a better experimental method to study the anti-depressive action of XueYiLe to the tail suspension and the forced swimming in mice. XueYiLe emulsion had significant anti-depressive for animal depression model in behavioral hopeless, because it can shorten the immobile time of the mice and decrease or at least not affect the autonomic activities of the mice. 2. Chronic unpredictable mild stress and isolated-living model is an ideal animal depression model. The XueYiLe emulsion can improve obviously behavioral index and show curative and preventative effect to the animal depression model. 3. XueYiLe emulsion can increase obviously the amount of monoamine neurotransmitter (NE, 5-HT, 5-HIAA) in the animal depression model, which may be one of the mechanisms of its anti-depressive action.
引文
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2. 丁素文,杨东华.浅谈抗抑郁药的发展趋势.黑龙江医药,2004;17(2):135～136
3. 张均田.神经药理学研究进展.北京:人民卫生出版社,2002;30
4. 李作平,赵 丁,任雷鸣等.合欢花抗抑郁作用的药理实验研究初探.河北医科大学学报,2003;24(4):214～216
5. 唐 瑛,蒋 璘.中草药提取物的抗抑郁作用研究概况.湖南中医药导报,2004;10(8):50～51
6. 卢艳花,谭仁祥.抗抑郁天然药的研究进展.中草药,2000;31(9):718
7. 张中启,袁 莉,罗质璞.积雪草提取物抑制小鼠体外单胺氧化酶 A 的活性.军事医学科学院院刊,2000;24(2):158
8. 陆 瑶,韩 婷,芮耀诚等.积雪草总苷对实验性抑郁症大鼠血清皮质酮和单胺类神经递质的影响.中药材,2005;28(6):492～496
9. 刘沐荣,韩 婷,陈 瑶等.羟基积雪草苷对小鼠抑郁行为和大鼠不同脑区单胺氧化酶活性的影响.中西医结合学报,2004;2(6):440～444
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