抑郁症神经生化和神经电生理学研究进展

抑郁症的发病机制复杂,神经生化学理论是迄今最为“肯定”、并被临床药理“充分利用”的,用以阐述抑郁症发病的神经生物学机制,抑郁症的发生不但与去甲肾上腺素(NE)、5-羟色胺(5-HT)水平相关;也可能与多巴胺(DA)、乙酰胆碱(Ach)、神经肽、γ-氨基丁酸(GABA)能系统等多种神经递质及受体的功能紊乱有关,还与内分泌系统和神经营养因子系统等方面的异常有关。同时,抑郁症的发生还可能与神经认知功能的缺损及神经电生理学的改变有关。     

哈蟆油石油醚提取物的抗抑郁作用

目的:探索哈蟆油石油醚部位(ROS)的抗抑郁作用及可能的机制.方法:雄性ICR小鼠,分为2批,每批均设空白对照组(生理盐水)和6个治疗组(分别给予阳性药氟西汀10 mg·kg-1和ROS不同剂量10,30,100,300,900 mg· kg-1),连续灌胃给药8d.第1批动物在第7天给药后1h和第8天给药后1h,分别采用小鼠强迫游泳和小鼠悬尾2种“行为绝望”抑郁动物模型进行行为学观察;行为学观察结束后小鼠眼球取血,用放射免疫法检测小鼠血清皮质酮(CORT)水平.第2批动物在第8天给药后采用利血平拮抗模型,观察ROS对由利血平引起小鼠体温下降和运动不能的影响.结果:ROS 100,300,900 mg· kg-1均能不同程度地缩短小鼠强迫游泳和悬尾不动时间(P＜0.05),能拮抗利血平致小鼠体温下降和运动不能(P＜0.05),降低小鼠血清皮质酮水平(P＜0.05).结论:ROS具有抗抑郁作用,其机制可能与单胺类神经递质以及下丘脑-垂体-肾上腺(HPA)轴密切相关.     

从莪术 虎杖两味中药探讨寒热药性对大鼠大脑不同部位单胺类神经递质的影响

目的:从中枢单胺类神经递质的含量差异探讨中药寒热药性的科学内涵。方法:将莪术、虎杖两味药性相反的中药给大鼠灌胃给药1个月后,用HPLC-ECD(高效液相色谱-电化学)法检测大鼠大脑不同部位单胺类神经递质的含量。结果:温热药莪术明显促进大鼠大脑不同部位单胺类神经递质的分泌,与空白组相比有统计学差异(P0.05,P0.01);寒凉药虎杖明显抑制大鼠大脑不同部位单胺类神经递质的分泌,与空白组相比有统计学差异(P0.05,P0.01)。结论:中药的寒热药性与中枢单胺类神经递质存在一定的相关性。     

反复心理应激大鼠血浆和下丘脑单胺神经递质的变化及加味四逆散的影响

目的 :观察反复心理应激大鼠血浆和下丘脑内DA、5 HT、E、NE的变化以及加味四逆散的影响。方法 :采用限制大鼠活动空间的方法造成反复心理应激的动物模型 ;血浆和下丘脑内DA、5 HT、E、NE含量测定采用电化学高效液相色谱分析方法。结果 :反复心理应激大鼠血浆DA、5 HT含量明显降低 ,NE、E含量则明显升高 ,下丘脑DA和 5 HT含量明显降低。加味四逆散可以升高应激大鼠下丘脑和血浆中DA、5 HT含量 ,并能降低血浆中NE、E含量 ,升高下丘脑和血浆 5 HT/NE以及血浆 5 HT/E ,作用优于人参总皂甙。结论 :加味四逆散可显著增强反复心理应激状态大鼠的抗应激能力 ,其机制与其升高中枢和血浆中 5 HT及DA含量 ,降低血浆中NE和E含量有关。     

解郁丸抗抑郁作用机制的初步研究

目的 :初步探讨解郁丸抗抑郁作用机制。 方法 :采用高剂量阿朴吗啡导致体温下降试验,5-羟色胺酸(5-HTP)诱导甩头行为试验以及高效液相色谱-电化学检测法测定小鼠下丘脑、皮层、海马等脑内单胺类递质及其代谢产物含量。 结果 :解郁丸能显著拮抗高剂量阿朴吗啡所致小鼠体温下降;增加5-HTP诱导甩头行为。解郁丸单次和连续14 d给药,可提高下丘脑中去甲肾上腺素(NE)、多巴胺(DA)与DA的代谢产物3,4-二羟基苯乙二醇(DOPAC)的比值;也可使皮层中5-HT,NE,5-HT的代谢产物5-羟吲哚乙酸(5-HIAA),DOPAC含量升高,降低5-HT与5-HIAA及DA与DOPAC的比值;并可提高海马中5-HT与5-HIAA及DA与DOPAC的比值。解郁丸可使利血平化小鼠下丘脑中NE,5-HIAA,海马中5-HT,5-HIAA,DA与DOPAC的比值明显升高。 结论 :解郁丸抗抑郁作用机制可能与调节不同脑区的5-HT,NE等神经递质有关。单次和连续14 d给药可增加不同脑区5-HT,NE,DA的含量,连续14 d给药对利血平化所致不同脑区单胺类递质含量下降也有不同程度的翻转效应。     

Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease

Neurodegeneration, a complex disease state, comprises several pathways that contribute to cell death. Conventional approach of targeting only one of these pathways has not been proven to be entirely successful and has demanded a hypothetical change as to how researchers design and develop new drugs. In this study, effects of a series of α, β‐unsaturated carbonyl‐based tetralone derivatives against Alzheimer's disease (AD) were investigated. Moreover, their activity toward amyloid β‐induced cytotoxicity was also studied. Six compounds including 3f , 3o , 3u , 3ae , 3af , and 3ag were discovered to be most protective against Aβ‐induced neuronal cell death in PC12 cells. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against MAO‐B, AChE, and self‐induced Aβ_1–42 aggregation. The compound 3f exhibited best AChE (IC₅₀ = 0.045 ± 0.02 μm ) inhibitory potential in addition to potent inhibition of MAO‐B (IC₅₀ = 0.88 ± 0.12 μm ). Furthermore, compound 3f disassembled the Aβ fibrils produced by self‐induced Aβ aggregation by 78.2 ± 4.8%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment.     

Evidences for the Involvement of Monoaminergic and GABAergic Systems in Antidepressant-like Activity of Tinospora cordifolia in Mice

The present study was taken up to investigate the effect of petroleum ether extract of Tinospora cordifolia (Wild.) Miers, on depression in mice. The extract (50, 100 and 200 mg/kg, p.o.) was administered for 14 successive days to Swiss young albino mice (either sex) and evaluated for antidepressant-like activity using tail suspension test and forced swim test. Petroleum ether extract at all three doses produced significant antidepressant-like effect in tail suspension test as well as in forced swim test and their efficacies were found to be comparable to imipramine (15 mg/kg, p.o.) and sertraline (20 mg/kg, p.o.). The extract at a dose of 50 mg/kg showed most potent effect and did not show any significant change in locomotor functions of mice as compared to control. The antidepressant-like effect of the extract was significantly reversed by pretreatment of animals with prazosin (a α(1)-adrenoceptor antagonist), sulpiride (a selective dopamine D(2)-receptor antagonist), p-CPA (a serotonin synthesis inhibitor) and baclofen (GABA-B agonist), when tested in tail suspension test. Moreover, petroleum ether extract also reduced the mouse whole brain monoamine oxidase (MAO-A and MAO-B) activities as compared to control, resulting in increase in the levels of brain monoamines. Therefore, the extract may have potential therapeutic value for the management of depressive disorders.     

罗布麻叶浸膏对脑内单胺类递质含量及细胞膜流动性的影响

罗布麻叶浸膏可使脑内5-HT及DA含量升高,其水溶性成分可使5-HT、5-HIAA及DA 含量升高,而NE含量降低,醇溶性成分上述作用更为明显。提示罗布麻叶浸膏可能含有兴奋中枢 5-HT神经元功能及抑制中枢肾上腺素神经元功能的化学物质,这些化学物质为水溶性及酸溶性。 脑神经细胞膜脂质流动性测定结果提示罗布麻叶浸膏水溶性部分可使膜流动性增加。     

司来吉兰对帕金森病模型大鼠黑质纹状体TH及GDNF表达的影响

目的观察司来吉兰对帕金森病(PD)模型大鼠黑质纹状体内酪氨酸羟化酶(TH)及胶质细胞源性神经营养因子(GDNF)表达的影响,探讨司来吉兰对多巴胺能神经元的保护作用及机制。方法 72只健康雄性SD大鼠随机分为对照组、模型组和司来吉兰组,每组均设4 d和8 d 2个亚组,各12只。模型组和司来吉兰组采用颈背部皮下注射鱼藤酮制备PD模型,对照组皮下注射等体积葵花油。之后司来吉兰组每日灌胃咪多吡0.5 mg/kg,模型组和对照组每日灌胃等体积生理盐水,4 d和8 d组分别连续灌胃4 d和8 d。采用免疫组化法和Western blotting法检测黑质纹状体TH和GDNF表达水平。结果免疫组化法和Western blotting法检测结果均显示,对照组大鼠黑质纹状体可见多量TH阳性细胞表达和少量GDNF阳性细胞表达,8 d和4 d组差异均无统计学意义。模型组TH和GDNF阳性细胞表达均明显低于对照组(均P<0.05),8 d和4 d组差异均无统计学意义。司来吉兰组TH阳性细胞表达低于对照组而高于模型组,GDNF阳性细胞表达高于对照组和模型组(均P<0.05),且8 d组均高于4 d组(均P<0.05)。结论司来吉兰可减轻PD模型大鼠黑质纹状体多巴胺能神经元的损伤,其作用机制可能与增加GDNF表达有关。     

Parathyroid surgery and methylene blue: A review with guidelines for safe intraoperative use

Methylene blue has been used to help facilitate parathyroid surgery for over 30 years. Its use has been widely considered both safe and cost effective. Twenty‐six cases of a toxic metabolic encephalopathy, however, have been reported with its use. As a result, some surgeons have stopped using this technique altogether. It is now known that methylene blue is a monoamine oxidase inhibitor. When combined with drugs that increase central serotonin neurotransmission, serotonin toxicity results. This is the cause of the encephalopathy described in the literature. A case report, review of the literature, and guidelines as to its proper use are presented so as to allow for safe parathyroid surgery. Laryngoscope, 2009