小补心汤总黄酮对获得性无助小鼠的抗抑郁作用及其对HPA轴功能的影响

目的采用小鼠获得性无助模型评价小补心汤总黄酮(XBXT-2)的抗抑郁作用,并探究在应激状态下,XBXT-2对下丘脑-垂体-肾上腺轴(HPA)功能的调节作用。方法采用电脑程序控制的穿梭箱条件反射系统,给予不可逃避的足底电击诱导获得性无助模型,经过穿梭箱回避程序筛选,将成功诱导无助行为的小鼠分为模型组、度洛西汀(Dlx,20mg·kg-1)组和XBXT-2(25,50 mg·kg-1)组,灌胃给药4 d,每日采用条件性回避反应测试程序,测定小鼠的逃避失败次数和逃避潜伏期。行为学检测结束后,采用酶联免疫吸附试验法检测血清皮质酮(CORT)和促肾上腺皮质激素(ACTH)水平、蛋白印迹法检测海马糖皮质激素受体(GRα/β)蛋白和脑源性神经营养因子(BDNF)的表达水平。结果亚慢性给予XBXT-2(25,50 mg·kg-1)可明显减少获得性无助小鼠逃避失败次数和(或)逃避失败潜伏期,在行为学有效基础上,亦可明显降低获得性无助小鼠血清CORT和ACTH水平,上调海马GRα/β蛋白和BDNF的表达。结论 XBTX-2在小鼠获得性无助模型中具有抗抑郁作用,作用机制可能与其抑制HPA轴功能亢进有关。     

新型5-HT1A受体激动和5-HT重摄取抑制双重活性化合物YL-0919抗抑郁作用的行为学评价

目的研究兼有5-HT1A受体激动和5-HT重摄取抑制双重活性化合物YL-0919的抗抑郁作用。方法分别采用小鼠悬尾实验、小鼠强迫游泳实验、小鼠自发活动实验和大鼠获得性无助模型,观察不同剂量（0.625、1.25、2.5和5mg/kg）YL-0919的抗抑郁作用。结果在小鼠悬尾实验和小鼠强迫游泳实验中,单次灌胃给予YL-0919（0.625～2.5mg/kg）能够显著缩短小鼠悬尾不动时间和游泳不动时间;在小鼠自发活动实验中,YL-0919在上述剂量范围对自发活动无影响;在大鼠获得性无助模型上,灌胃给予YL-0919〔0.625～1.25mg/（kg·d）,1~4d〕能显著减少逃避失败次数。结论 YL-0919在小鼠和大鼠模型上具有明确的抗抑郁活性,并且在抗抑郁的有效剂量范围内无中枢兴奋和抑制作用,具有成为新型抗抑郁药物的研发潜力。     

棉籽总黄酮抗抑郁作用的研究

目的探讨棉籽总黄酮(代号:CTN-T)抗抑郁活性。方法采用小鼠悬尾模型、大小鼠强迫游泳模型、5-羟色氨酸(5-hydroxy-L-tryptophan,5-HTP)诱导小鼠甩头模型、小鼠育亨宾毒性增强模型探讨CTN-T的抗抑郁活性及其可能作用环节。结果小鼠悬尾实验中,CTN-T单次灌胃160~320mg.kg-1或连续4 d(每天2次)灌胃60 mg.kg-1缩短悬尾不动时间;在小鼠强迫游泳实验中,CTN-T连续7 d灌胃给药(每天2次)在40~60 mg.kg-1缩短游泳不动时间;在大鼠强迫游泳实验中,CTN-T连续4 d灌胃(每天2次)20~60mg.kg-1缩短游泳不动时间;此外,小鼠单次灌胃CTN-T160 mg.kg-1或连续4 d(每天2次)灌胃80 mg.kg-1增强5-HTP诱导的甩头行为。而小鼠连续4 d灌胃CTN-T 60~180 mg.kg-1对育亨宾毒性均无影响。结论CTN-T有抗抑郁活性,可能与其增强脑内5-HT神经功能有关。     

巴戟天寡糖对鼠强迫性游泳和获得性无助抑郁模型的影响

为了深入和全面地评价巴戟天寡糖 (MOs)的抗抑郁作用 ,本研究观察了不同批次的MOs对大鼠 ,小鼠强迫性游泳和大鼠获得性无助抑郁模型的影响 .结果显示 ,3批MOs在 2 0～ 5 0mg·kg- 1(ip或po)剂量范围内显著缩短大鼠和小鼠强迫性游泳期间的不动时间 ,其剂量效应均显示行为药理学所特有的U型曲线 .不同批次的MOs有效剂量均非常接近 .在大鼠获得性无助抑郁模型 ,MOs 6 0～ 10 0mg·kg- 1(ip ,每天 2次 ,连续 8次 )显著减少大鼠的逃避失败次数 ,6 0mg·kg- 1还明显减少逃避失败动物数 .这些结果进一步表明MOs具有抗抑郁作用     

丹参酮的抗抑郁作用研究

目的：研究丹参酮的抗抑郁作用。方法：丹参酮灌胃给药。通过尾静脉注射利血平（2mg·kg-1）复制小鼠抑郁模型,观察眼帘下垂动物数、运动不能动物数,测肛温;腹腔注射丁苯那嗪（40mg·kg-1）复制小鼠抑郁模型,观察眼帘下垂动物数和僵住动物数;尾静脉注射利血平（2mg·kg-1）后进行悬尾、强迫游泳实验,复制小鼠获得性绝望模型,观察小鼠悬尾不动时间和游泳不动时间;通过静脉注射单胺氧化酶抑制剂（盐酸色胺）复制大鼠惊厥模型,观察大鼠动作平均分值、拍打动作持续时间。结果：60、30、20mg·kg-1丹参酮可显著减少利血平复制的抑郁模型小鼠眼帘下垂、运动不能动物数,显著升高模型小鼠肛温（P〈0.05）;60、30mg·kg-1丹参酮可显著减少丁苯那嗪复制的抑郁模型小鼠眼帘下垂、僵住动物数（P〈0.01或P〈0.05）;60、30mg·kg-1丹参酮可显著缩短绝望模型小鼠悬尾不动、游泳不动时间（P〈0.01）;42、21、14mg·kg-1丹参酮可显著降低盐酸色胺复制的惊厥模型大鼠动作平均分,42、21mg·kg-1丹参酮可显著缩短模型大鼠拍打动作持续时间（P〈0.01或P〈0.05）。结论：丹参酮有一定抗抑郁作用。     

小补心汤总黄酮提取物对慢性应激模型大鼠的抗抑郁作用

目的古代文献记载小补心汤(XBXT,由代赭石、旋覆花、竹叶和淡豆豉4味中药组成)有缓解抑郁情绪的作用。应用大鼠慢性应激模型探讨XBXT总黄酮(XBXT-2)的抗抑郁作用及可能机制。方法连续28d给予大鼠一系列慢性不可预测性的刺激建立慢性应激模型,同时给予XBXT-2(25或50mg·kg-1·d-1,ig)或丙米嗪(10mg·kg-1·d-1,ig),采用蔗糖饮水实验、开场活动实验和新奇抑制摄食实验观察抗抑郁行为效应;采用酶联免疫吸附实验检测血清皮质酮含量,Western蛋白印迹法检测海马糖皮质激素受体(GR)α/β、脑源性神经营养因子(BDNF)、磷酸化cAMP反应元件结合蛋白(p-CREB)、细胞外信号调节激酶(ERK1/2)及其磷酸化形式(p-ERK1/2)蛋白表达水平。结果XBXT-2或丙米嗪可逆转慢性应激大鼠蔗糖饮水偏嗜度降低、自发活动减少及新奇抑制摄食潜伏期延长,显著降低应激大鼠血清皮质酮含量,上调海马GRα/β,BDNF,p-CREB和p-ERK1/2蛋白表达。结论XBXT-2对慢性应激大鼠具有抗抑郁作用,其机制可能与抑制下丘脑-垂体-肾上腺轴的过度激活,上调海马BDNF相关的神经营养通路中蛋白表达有关。     

电针百会穴对获得性无助大鼠抑郁样行为和血清CORT及ACTH的影响

目的探讨电针治疗抑郁症的机制。方法将32只SD大鼠随机分为正常组、模型组、假针组和电针组,通过给予不可逃避足底电击诱导无助样行为和给予可逃避的足底电击检测无助行为制备获得性无助亚急性抑郁动物模型,电针组给予连续5 d百会穴电针,假针组在穴位旁给针但不通电。检测大鼠的行为变化,用酶联免疫吸附试验(ELISA)法检测血清皮质酮(CORT)和促肾上腺皮质激素(ACTH)水平。结果与正常组比较,造模后模型组、假针组和电针组大鼠的强迫游泳挣扎时间显著下降(P<0.01),敞箱试验水平总位移和直立次数均显著减少(P<0.01);给予电针治疗后,与模型组比较,电针组大鼠的强迫游泳挣扎时间显著升高(P<0.01),敞箱试验水平总位移和直立次数均显著增加(P<0.01),而且电针组大鼠血清CORT和ACTH水平显著低于模型组(P<0.01)。结论获得性无助抑郁大鼠表现出下丘脑-垂体-肾上腺皮质(HPA)轴功能亢进,应用电针可产生抗抑郁效应,电针可能是通过拮抗HPA轴功能亢进而发挥其抗抑郁作用。     

左旋薄荷酮抗抑郁作用及机制研究

目的：研究左旋薄荷酮（MTN）的抗抑郁作用及可能机制。方法：以开野实验、强迫游泳实验、悬尾实验、糖水偏好实验对ICR小鼠进行行为学观察,探讨左旋薄荷酮对抑郁模型小鼠行为学的改善作用,同时检测小鼠血清皮质酮及皮质中糖皮质激素受体（GR）、脑源性神经营养因子（BDNF）含量的变化。结果：左旋薄荷酮15、30 mg·kg-1能显著缩短小鼠强迫游泳、悬尾不动时间,显著提高慢性不可预知温和刺激（CUMS）小鼠糖水偏好值,并能显著降低CUMS小鼠血清皮质酮含量、升高GR mRNA和BDNF的表达。结论：左旋薄荷酮具有抗抑郁作用,其抗抑郁机制可能与抑制下丘脑-垂体-肾上腺轴（HPA轴）过度活化、促进皮质BDNF的表达有关。     

GL-21抗抑郁的药效初探

目的：初步评价GL-21的抗抑郁药效,并探讨其可能的优势。方法：采用小鼠悬尾试验模型和小鼠强迫游泳试验模型初步评价抗抑郁效果。小鼠自发活动实验评价其兴奋作用。小鼠育亨宾毒性增强实验探讨其可能的作用机制。大鼠阴茎勃起实验,考察其对性功能的改善作用。结果：GL-21（1、2、4、8 mg·kg-1）可显著减少悬尾和强迫游泳试验的不动时间（P<0.01或P<0.05）,且不显著增加小鼠自发活动的总路程。GL-21（2、4、8 mg·kg-1）显著增强育亨宾毒性,增加小鼠死亡。剂量低至1.25 mg·kg-1（sc）可显著诱导大鼠阴茎勃起。结论：GL-21可能具有抗抑郁作用且改善性功能障碍。     

五羟基色氨酸对抑郁症的影响及其机制

目的:研究5-羟基色氨酸(5-HTP)抗抑郁的机制。方法:小鼠每天分别灌胃给予5-HTP(50,100,200 mg.kg-1),盐酸氟西汀阳性对照组每天灌胃给予5 mg.kg-1,连续给药7 d,采用小鼠悬尾实验、强迫游泳实验观察5-HTP对动物行为学的影响。慢性应激性抑郁模型中5-HTP和盐酸氟西汀连续给药21 d后观察5-HTP对动物行为学的影响。采用ELISA方法检测小鼠脑组织5-HT水平,以及小鼠血清中TNF-α和IL-6水平。结果:给予5-HTP可明显缩短小鼠悬尾及强迫游泳实验中的不动时间,同时较高浓度5-HTP可显著增强小鼠脑组织5-HT水平,5-HTP还可降低血清中TNF-α和IL-6水平。结论:5-HTP有抗抑郁作用,在升高脑内5-HT的同时,还可降低体内细胞因子的产生,这可能是其改善抑郁症状的机制之一。     

The total flavonoids extracted from Xiaobuxin Tang reverse the hyperactivity of hypothalamic-pituitary-adrenal axis in chronically stressed rats

Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal(HPA)axis in chronic mild stress(CMS)model of rats.Methods Using ELISA to test the serum corticosterone,adrenocorticotropic hormone(ACTH)and corticotropin-releasing hormone(CRH)level in CMS rats;Using western blot to determine hippocampal glucocorticoids receptors(GR)expression in CMS rats.Results Co-administration of XBXT-2(25,50 mg·kg-1,p.o.,28 days,the effective doses for behavioral responses)significantly decreased the serum corticosterone and ACTH level in CMS rats,while the CRH level was not markedly affected by chronic stress or drugs.Moreover,XBXT-2 significantly increased the GR expression in the hippocampus of CMS rats.The same effects were observed in the positive control drug imipramine(10 mg·kg-1,p.o.).Conclusions The decrease of serum corticosterone and ACTH level,as well as the increase of hippocampal GR expression may be the mechanisms underlying the antidepressant action of XBXT-2,which may associate with HPA axis.     

Role for serotonin in the antidepressant-like effect of a flavonoid extract of Xiaobuxin-Tang

Xiaobuxin-Tang (XBXT), a traditional Chinese herbal decoction, has been used for the treatment of depressive disorders for centuries in China. Herein, we explored the antidepressant-like effect and its monoaminergic mechanism of the total flavonoids (XBXT-2) isolated from the extract of XBXT. In present study, single XBXT-2 (25, 50, 100 mg/kg, p.o.) administration significantly potentiated the mouse head-twitch response induced by 5-hydroxytryptophan (5-HTP, a metabolic precursor to serotonin), and also, decreased the immobility time in mouse tail suspension test, which was completely prevented by p-chlorophenylalanine (PCPA, an inhibitor of serotonin synthesis) pretreatment. However, single treatment with XBXT-2 had no effect on yohimbine toxicity and high dose of apomorphine-induced hypothermia in mice. These results indicated that acute treatment with XBXT-2 produced serotonergic, but not noradrenergic activation. In addition, chronic XBXT-2 (25, 50 mg/kg, p.o., 28 days) treatments significantly reversed the depressive-like behaviors in chronically mildly stressed (CMS) rats, including the reduced sucrose preference, deficient locomotor activity and prolonged latency to novelty-suppressed feeding. Furthermore, XBXT-2 normalized the neurotransmitter changes, including the decreased serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) levels in hippocampus and prefrontal cortex in CMS rats. These findings confirm the antidepressant-like effect of XBXT-2 in CMS model of rats, which may be primarily based on its serotonergic activation.     

菊淀粉型六聚糖对鼠强迫性游泳和低速率差式强化程序的影响

目的确定巴戟天中菊淀粉型六聚糖单体（ＩＨＳ）的抗抑郁作用。方法采用经典大小鼠强迫性游泳和程序化大鼠低速率差式强化（ＤＲＬ ７２ｓ）法。结果在小鼠强迫性游泳模型上,ｐｏ ＩＨＳ ８０ ｍｇ·ｋｇ－１与 ｉｐ地昔帕明 １０ ｍｇ·ｋｇ－１的作用类似,能明显缩短小鼠的不动时间;同样,ｐｏ ＩＨＳ ２０ｍｇ·ｋｇ－１也缩短大鼠强迫性游泳的不动时间,其效果与加地昔帕明 ４０ ｍｇ·ｋｇ－１相当。另外,在大鼠 ＤＲＬ ７２ｓ模型上,ｉｇ ＩＨＳ ５～１０ｍｇ·ｋｇ－ｌ和地昔帕明 ５ ｇ·ｋｇ－１,均增加大鼠ＤＲＬ－ ７２ｓ的强化数。结论 ＩＨＳ具有抗抑郁作用,是巴戟天中抗抑郁有效成分。     

Anti-emetic mechanisms of Xiaobanxia Tang decoction on the chemotherapy-induced pica model in rats

OBJECTIVE To investigate the mechanisms of Xiaobanxia Tang(XBXT)in the prevention and treatment of chemotherapy-induced nausea and vomiting.METHODS The chemotherapy-induced rat pica model was established by intraperitoneal injection of cisplatin 6mg·kg-1.Kaolin consumption was used as an indicator of nausea and vomiting.Wistar male rats were randomly divided into normal control,XBXT normal control,model,ondansetron treating,XBXT decoction high and low dose groups.The rats in ondansetron group,XBXT normal control group,XBXT high and low dose groups were gavaged ondansetron 2.6mg·kg-1·d-1,XBXT 1.6,3.2and 1.6g·kg-1·d-1,respectively 1hbefore cisplatin injection,and the administration were given every 12 h.Kaolin consumptions were weighed every 12 h.After 24 hand 72hof cisplatin injection,animals were sacrificed respectively.The contents of 5-HT,5-HIAA,dopamine(DA),DOPAC,substance P(SP),TPH,MAO and TH were measured by ELISA.The mRNA expression of 5-HT transporter(SERT),5-HT3 Areceptor,SP precursor(PPTA),NK1 and D2receptors in rat ileum and medulla oblongata were measured by RT-PCR,the protein expression were measured by Western blotting.RESULTS The high and low dosages of XBXT could significantly inhibit kaolin consumptions in cisplatin-treated rats,and reduce5-HT,increase 5-HIAA contents and reduce 5-HT3 Areceptor mRNA and protein expression,above effects are related to the reduction of TPH and the enhancement of MAOA levels.The two dosages of XBXT could significantly reduce SP and NK1 mRNA and protein expression,which was related to the reduction of PPTA mRNA expression.XBXT could also significantly reduce DA contents and D2 receptor mRNA and protein expression,which was related to the reduction of TH.CONCLUSION XBXT has significant antiemetic effect in chemotherapy-induced nausea and vomiting,the underlying mechanisms are related to the inhibition of 5-HT and5-HT3 Areceptor,SP and NK1 receptor,DA and D2 receptor.     

枳苓六妙口服液对疲劳雄性大鼠血睾酮及相关激素的影响

目的：观察枳苓六妙口服液对疲劳雄性大鼠作用。方法：采用高（360 mg·kg~（-1））、中（118.3 mg·kg~（-1））、低（59.2mg·kg~（-1））不同剂量枳苓六妙口服液给正常wistar雄性大鼠连续灌胃6周,在给药2周、4周、6周后三个时间段,测定其力竭游泳时间和负重运动后雄性大鼠睾酮（T）、皮质酮（C）、促卵泡生成素（FSH）、促黄体生成素（LH）、雌二醇（E_2）和促肾上腺皮质激素（ACTH）的浓度。结果：与对照组比较,枳苓六妙口服液高、中剂量组在3周后均能明显延长雄性大鼠负重游泳时间（P〈0.05或0.01）;6周后,各组均能明显提高雄性大鼠血T浓度和LH浓度（P〈0.05）;高、中剂量组均能显著降低血中C水平（P〈0.05）;6周后,高剂量组能提高雄性大鼠FSH的浓度,差异有统计学意义（P〈0.05）;各剂量组对ACTH和E_2没有明显影响（P〉0.05）。结论：枳苓六妙口服液中、高剂量组具有显著的抗疲劳作用,血清睾酮水平降低可能是疲劳发病机制的重要环节。     

Effect of the selective 5-HT7 receptor antagonist SB 269970 in animal models of anxiety and depression

The aim of the present study was to examine the effect of the selective 5-HT7 receptor antagonist SB 269970 (0.25-20 mg/kg) in the behavioral tests commonly used for predicting anxiolytic- and antidepressant-like activity. Diazepam and imipramine were used as standard drugs. SB 269970 (in one medium dose of 0.5 or 1 mg/kg) exerted a specific antianxiety-like effect in the Vogel drinking test in rats, in the elevated plus-maze test in rats and in the four-plate test in mice. Moreover, SB 269970 (in one medium dose of 5 or 10 mg/kg) showed antidepressant-like activity in the forced swimming and the tail suspension tests in mice. At the same time, the tested compound at doses of 1-20 mg/kg did not change the spontaneous locomotor activity of mice. The potential anxiolytic and antidepressant effects produced by SB 269970 were weaker than those of the reference drugs employed. It is noteworthy that the active doses of SB 269970 were devoid of any visible motor side-effects. In conclusion, the results of our studies indicate that 5-HT7 receptor antagonists may play a role in the therapy of both anxiety and depression.     

不同剂量的重组人血管内皮抑素腹腔给药对腹水瘤小鼠的疗效观察

目的 观察不同剂量重组人血管内皮抑素(恩度)对腹水瘤小鼠腹水疗效的差异.方法 建立腹水瘤小鼠模型.将160只小鼠随机分成5组,每组32只,依次给予相同体积的生理盐水(Control组)、12.5 mg·kg-1恩度、25 mg·kg-恩度、50 mg·kg-恩度、100 mg·kg-1恩度,隔天给药.记录各组小鼠的体质量、腹围及生存期,观察腹水的性状,检测腹膜通透性.结果 (1)第7天各组随机解剖13只小鼠检测腹膜通透性,观察到小鼠腹水发生率为80％;(2)体质量方面,仅100 mg·kg-1剂量组与Control组的差异有统计学意义(P＜0.05),余剂量组比较均差异无统计学意义(P＞0.05);(3)腹围方面,对比Control组,50 mg·kg-1和100 mg·kg-1剂量组比较差异有统计学意义(P＜0.05),余剂量组比较均差异无统计学意义(P＞0.05);(4)随着恩度剂量增加,血性积液程度整体上呈减少趋势;(5)与Control组相比,各恩度剂量组的生存期、540 nm波长处Evan蓝的吸光度(OD540)值的比较均差异无统计学意义(P＞0.05).结论 恩度对血性积液的效果与剂量相关.50、100 mg·kg-1剂量组相对其余剂量组腹水抑制作用明显,为恩度腔内治疗的有效剂量.     

花椒多酚类化合物急性给药的抗抑郁作用及机制研究

目的探讨花椒多酚类化合物总提取物（ZPPC）急性给药对ICR小鼠抑郁模型的拮抗作用及可能的机制。方法采用经典的行为绝望抑郁模型,即小鼠悬尾实验和强迫游泳实验,观察ZPPC急性给药对应激小鼠绝望不动时间的影响;同时观察ZPPC对小鼠自主活动的影响,采用荧光分光光度法测定ZPPC对小鼠脑内单胺氧化酶活性的影响。结果与空白组比较,ZPPC（50,100,200mg·kg-1,i.g.）明显缩短小鼠悬尾和强迫游泳实验中的不动时间,其作用类似于阳性对照药丙咪嗪（10mg·kg-1,i.p.）;ZPPC还明显抑制脑内单胺氧化酶的活性。结论 ZPPC急性给药在小鼠行为绝望模型中显示出明显的抗抑郁作用,其作用机制可能与抑制脑内单胺氧化酶活性有关。