培元解郁方对急性糖皮质激素诱导SD大鼠的抗抑郁作用及TRY-KYN代谢途径的调节

目的:研究培元解郁方的抗抑郁作用以及对色氨酸(TRY)-犬尿氨酸(KYN)代谢的调节机制。方法:建立氢化可的松大鼠抑郁模型,以蔗糖消耗反映大鼠的抑郁状态,采用高效液相-质谱联用(HPLC-MS/MS)技术检测脑组织KYN、TRY、喹啉酸(QUIN)、犬尿烯酸(KA)含量,实时荧光定量PCR技术测定肝组织中色氨酸2,3-双加氧酶(TDO)mRNA表达水平和脑组织海马中吲哚胺2,3-双加氧酶(IDO)、5-HT1A的mRNA表达。结果:造模21 d后,大鼠对蔗糖的偏好降低,KYN/TRY比值升高,QUIN含量升高,KA含量降低,TDO mRNA的表达水平增加,5-HT1AmRNA的表达水平降低,差异有统计学意义(P0.05)。各给药组能提高大鼠对蔗糖的偏好,差异有统计学意义(P0.05)。各给药组均能显著降低KYN/TRY比值,差异有统计学意义(P0.05),培元解郁方中剂量组和天丝饮组能显著提高KA的含量,降低QUIN的含量,差异有统计学意义(P0.05)。天丝饮能明显降低肝脏中TDO和海马中IDO mRNA的表达,差异有统计学意义(P0.05)。四逆散和培元解郁方中、高剂量能够增加海马中5-HT1AmRNA的表达,差异有统计学意义(P0.05)。结论:天丝饮、四逆散和培元解郁方均有抗抑郁药样作用,机制与降低TRY-KYN代谢的关键酶mRNA表达,降低神经毒性代谢产物和增加神经保护性代谢产物,从而提高神经元保护作用,以及增加5-HT1A的mRNA表达有关。     

Antidepressant-like effects of aniracetam in aged rats and its mode of action

RATIONALE: Conventional as well as newer antipsychotics cause weight gain, and, in the regulation of body weight, both insulin and leptin are hormones involved. OBJECTIVE: The aim of the present study was to compare these hormonal levels in patients on treatment with different antipsychotics. METHODS: Nineteen patients receiving conventional antipsychotics, 14 patients receiving clozapine and 14 patients receiving olanzapine, were studied. Fasting blood samples for insulin, leptin, glucose, and drug serum concentrations were analyzed. In addition, body mass index (BMI) was calculated. RESULTS: The median insulin level was significantly higher in the patients receiving olanzapine than in those receiving conventional agents, whereas there was no significant difference in insulin between the clozapine and the other two groups. However, in the clozapine group, insulin levels were positively correlated to the drug serum concentration. BMI was elevated in about half of the patients, with no difference being found between the groups. The leptin level was significantly higher in the women than in the men in the conventional agent group, but not in the olanzapine or clozapine groups. CONCLUSIONS: The higher insulin level in the patients receiving olanzapine than in those receiving conventional antipsychotics, despite similar BMI, points to a probable influence of olanzapine on insulin secretion. The correlation between the insulin levels and the clozapine concentration indicates, in addition, an influence of clozapine on insulin secretion. The gender difference in leptin, i.e. females normally having higher leptin levels than males, was found in the conventional agent group, but not in the olanzapine or clozapine groups, suggesting that also leptin regulation is altered during olanzapine or clozapine treatments. Moreover, it was mainly due to an increase of leptin in the males that leptin levels were equalized between sexes in the olanzapine group. We conclude that the influence of olanzapine and clozapine on both insulin and leptin levels might be associated with their weight-gain-inducing ability, while other mechanisms may be involved in the weight gain caused by conventional antipsychotics.     

首发儿童精神分裂症患者母亲抑郁症的调查

为探讨独生男孩首次患精神分裂症后,其母伴抑郁症状的临床特点,对38例患儿母亲进行症状自评量表(SCL-90)、抑郁自评量表(SDS)和汉密尔顿抑郁量表(HAMD)评定。同时选取年龄、文化程度、职业相匹配的38例健康独生男孩的母亲为对照。结果:研究组常伴有抑郁症状,三种量表总分均明显高于对照组(P<0.001)。提示,对伴抑郁症状(患儿)母亲应予心理和抗抑郁药物治疗,对存在心身健康问题(患儿)母亲给予咨询、指导和社会心理支持。     

肠舒通胶囊的药效学研究

目的：通过对肠舒通胶囊的药效学研究,确证其应用于便秘和抑郁症治疗的效果。方法：以正常动物致泻试验、燥结型便秘模型动物致泻试验、小鼠小肠及大鼠大肠推进试验验证肠舒通胶囊用于便秘治疗的效果;以小鼠和大鼠强迫性游泳试验验证肠舒通胶囊的抗抑郁效果。结果：肠舒通胶囊能增加正常和燥结型便秘模型小鼠的粪便粒数与重量,不论是对正常动物还是燥结型便秘模型动物均可产生一定程度的致泻作用,可软化大便;能促进小鼠小肠和大鼠大肠炭末推进百分率。在两种动物抑郁行为模型上,特定剂量的肠舒通口服后可显示出抗抑郁作用。结论：肠舒通可增加胃肠蠕动,促进排便,适于慢性功能性便秘治疗,值得推广,尤其适于老年人。并且在抑郁症治疗上具有潜在应用价值。     

60例维持性血液透析患者抑郁障碍调查及相关因素分析

目的探讨维持性血液透析患者产生抑郁障碍的机率、相关因素及药物干预的效果。方法应用抑郁的诊断标准及抑郁自评量表(SDS)对60例无精神病病史的维持性血液透析患者进行诊断及评分,根据评分结果将患者分成抑郁组和非抑郁组。比较两组患者性别、年龄、文化程度、透析时间、就业率、医疗付费方式、营养状态和顺应性的差异。同时,对有抑郁障碍的患者予百忧解抗抑郁治疗,观察抗抑郁治疗的疗效。结果18.3%的血透患者有抑郁障碍;两组患者的年龄、性别、文化程度、透析时间比较均无显著性差异;抑郁组中不顺应者、自费率、营养不良发生率、糖尿病肾病(DN)的比率均显著高于非抑郁组,而就业率却低于非抑郁组;百忧解治疗后患者的睡眠障碍、对日常生活丧失兴趣,无愉快感及自责和内疚感等三项症状改善较为明显。结论血液透析患者产生抑郁障碍的机率较高;血液透析患者抑郁障碍与患者的营养不良、顺应性下降、自费、低就业率及糖尿病等因素有关;抗抑郁药物治疗维持性血液透析患者的抑郁障碍有一定疗效。     

匝迪-5味丸对急性应激所致行为绝望小鼠的抗抑郁作用研究

目的初步观察匝迪-5味丸的抗抑郁作用。方法通过小鼠悬尾实验(TST)、小鼠强迫游泳实验(FST)及利血平致小鼠抑郁模型,并以盐酸氟西汀为对照,观察连续7 d给匝迪-5味丸后对急性应激所致行为绝望小鼠的影响及腹腔注射利血平诱发抑郁模型小鼠的眼睑下垂、运动不能及体温变化的影响。结果与空白组比较,阳性对照组、匝迪-5味丸高、中剂量组均能缩短小鼠TST不动时间(P0.01);与空白组比较,阳性对照组,匝迪-5味丸高、中、低剂量组均能缩短小鼠FST不动时间(P0.05或P0.01)。与模型组比较,阳性对照组,匝迪-5味丸的高、中、低剂量组明显对抗利血平所致小鼠眼睑下垂、运动不能及体温降低(P0.05或P0.01)。结论匝迪-5味丸能改善急性应激所致行为绝望小鼠及利血平诱导小鼠抑郁状态,其作用机制值得进一步研究。     

Microinjection of sanguinarine into the ventrolateral orbital cortex inhibits Mkp-1 and exerts an antidepressant-like effect in rats

We investigated the antidepressant effects of bilateral intra-the ventrolateral orbital cortex (VLO) administration of sanguinarine (SA), a selective mitogen-activated protein kinase phosphatase-1 (Mkp-1) inhibitor, in rats that had been subjected to a forced swimming test (FST) which is a classic animal model of depression. The expression of Mkp-1 and activation of ERK (ratio of phosphor-ERK to ERK) were also examined by immunoblotting. A single bilateral intra-VLO infusion of SA (2.5, 5 or 10 μg/0.5 μl per side) significantly reduced immobility time in the FST in dose-dependent fashion, as compared to vehicle-treated controls. A similar antidepressant effect was also observed in rats systemically administered fluoxetine, a classic antidepressant. The effects observed in the FST could not be attributed to non-specific increases in activity as neither microinjection of SA into the VLO nor fluoxetine treatment altered the behavior of the rats during the locomotion test. In addition, a decrease in the expression of Mkp-1 and a correlative increase in ERK activation were involved in the antidepressant effects of the bilateral SA administration into the VLO. The results indicated that Mkp-1 within the VLO is involved in the process of depression and may be a potential target for therapeutic action of antidepressant treatment.     

远志醇提物对抑郁症模型小鼠的保护作用研究

目的:研究远志醇提物对抑郁症模型小鼠的保护作用。方法:通过小鼠悬尾实验、强迫游泳实验、慢性不可预知性应激+开场实验分析远志醇提物的抗抑郁作用。各小实验中雄性小鼠均分为模型对照(等容生理盐水)、氯米帕明(20mg·kg-1)和远志醇提物高、中、低剂量(10、5、2.5g·kg-1)组。结果:高、中、低剂量远志醇提物均可缩短抑郁症模型小鼠悬尾不动时间、游泳不动时间和增加移动格数。结论:远志醇提物对模型小鼠抑郁症状态有一定的改善作用。     

Prognostic value of exercise capacity among patients with treated depression: The Henry Ford Exercise Testing (FIT) Project

Background

Exercise capacity is associated with survival in the general population. Whether this applies to patients with treated depression is not clear.

Hypothesis

High exercise capacity remains associated with lower risk of all‐cause mortality (ACM) and nonfatal myocardial infraction (MI) among patients with treated depression.

Methods

We included 5128 patients on antidepressant medications who completed a clinically indicated exercise stress test between 1991 and 2009. Patients were followed for a median duration of 9.4 years for ACM and 4.5 years for MI. Exercise capacity was estimated in metabolic equivalents of tasks (METs). Cox proportional hazards regression models were used.

Results

Patients with treated depression who achieved ≥12 METs (vs those achieving <6 METs) were younger (age 46 ± 9 vs 61 ± 12 years), more often male (60% vs 23%), less often black (10% vs 27%), and less likely to be hypertensive (51% vs 86%), have DM (9% vs 38%), or be obese (11% vs 36%) or dyslipidemic (45% vs 54%). In the fully adjusted Cox proportional hazard regression model, exercise capacity was associated with a lower ACM (HR per 1‐MET increase in exercise capacity: 0.82, 95% CI: 0.79–0.85, P < 0.001) and nonfatal MI (HR: 0.92, 95% CI: 0.87–0.97, P = 0.004).

Conclusions

Exercise capacity had an inverse association with both ACM and nonfatal MI in patients with treated depression, independent of cardiovascular risk factors. These results highlight the potential impact of assessing exercise capacity to identify risk, as well as promoting an active lifestyle among treated depression patients.     

盐酸曲唑酮治疗早泄临床观察

目的探讨早泄患者使用盐酸曲唑酮治疗的效果。方法对60位患者随机分为实验组和对照组,两组以相同的服药方式分别服用盐酸曲唑酮及安慰剂,一个疗程后评价疗效。结果实验组患者治疗率78%,治疗有效率为93%。结论盐酸曲唑酮治疗勃起功能障碍及早泄明显有效,特别是年轻患者疗效更佳。