目的探讨慢性温和应激对大鼠血管内皮功能的影响及其作用机制。方法采用孤养与慢性轻度不可预见性应激模型相结合建立慢性温和应激动物模型,随机分为实验组和对照组,采用ELISA法检测两组大鼠血清皮质醇、细胞间黏附因子1(ICAM-1)、白介素6(IL-6)、血浆内皮素1(ET-1)的含量,透射电镜观察大鼠血管内皮超微结构的改变。结果实验组大鼠第2周和第3周体质量显著低于对照组(P0.05);血清皮质醇的含量显著增加(P0.05);血清ICAM-1、IL-6、血浆ET-1均较对照组明显升高(P0.05);血管内皮超微结构改变明显。结论慢性温和应激可导致大鼠血管内皮功能损伤。

Objective To study the endothelial function damage of rat under chronic stress.Methods En-zyme linked immunosorbent assay (ELISA)was applied to determining plasma levels of ET-1,serum lev-els of IL-6,ICAM-1,Cortisol.The Vascular endothelial morphological changes were identified via trans-mission electron microscope.Results From the second week,the body weight of rats in the experimental group were significantly lower than the control group (P <0.05).A significant increase in serum cortisol (P <0.05).The content of ICAM-1,IL-6,plasma ET-1 levels were higher in experimental group than in controlled group (P <0.05).Ultrastructural of Vascular endothelial were changed significantly.Conclu-sion Chronic mild stress can lead to vascular endothelial dysfunction in rats.

本文旨在探讨慢性应激性抑郁发生过程中眶额叶多巴胺D1受体对谷氨酸(glutamic acid,Glu)及其N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体的NR2B亚基的影响。实验通过建立慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)抑郁模型,结合眶额叶微量注射多巴胺D1受体激动剂SKF38393和多巴胺D1受体拮抗剂SCH23390,运用糖水偏爱测试、悬尾实验和敞箱实验等方法检测动物的行为表现,采用高效液相色谱法(high-performance liquid chromatography,HPLC)和蛋白质免疫印迹法(Western blot,WB)来检测眶额叶内谷氨酸、多巴胺含量及NR2B和多巴胺D1受体的表达。结果显示,与对照组相比,CUMS组大鼠表现出明显的抑郁样行为变化,且眶额叶多巴胺含量降低,其D1型受体表达降低,谷氨酸含量升高,其NMDA受体的NR2B亚基也明显上调;注射SKF38393后可明显改善应激引起的抑郁样行为,且眶额叶谷氨酸含量显著下降,NMDA受体的NR2B亚基表达也有所降低;正常大鼠注射多巴胺D1受体拮抗剂SCH23390,大鼠表现出和CUMS模型组相似的抑郁样行为,且眶额叶谷氨酸含量升高,其NMDA受体的NR2B亚基也明显上调。以上结果表明,慢性不可预见性应激可能使眶额叶多巴胺释放减少,从而使谷氨酸过量释放,NMDA受体过度激活,导致抑郁发生。多巴胺抗抑郁作用是通过D1型受体抑制谷氨酸及其NMDA受体NR2B亚基表达来实现。

Stressors play a pivotal role in the occurrence of depressive illnesses. Disorders of monoamine neurotransmitters and their receptors may be the fundamental causes of depression. Additionally, abnormal expression of glutamic acid (Glu) and its receptor may be a major reason for depression. Consequently, the study of the relationship between monoamine and glutamic acid neurotransmitter in stress-induced depression has significances to reveal the profound mechanism of depression. NR2B subunits which are highly expressed in the cortex, hippocampus and olfactory bulb, are one of the key subunits of NMDA receptors. Orbital frontal cortex (orbital frontal cortex, OFC), which plays a significant role in higher brain function, such as emotional and complex behavior, is one of the major sub-regions of prefrontal. This study was to investigate the effect of orbital frontal cortex D1 dopamine receptor on Glu and its receptors, especially on NR2B subunits of N-methyl-D-aspartic acid (NMDA) recepto

为了研究慢性应激性抑郁发生中海马转化生长因子β1（transforming growth factor beta ！1， TGF-β1）和硒蛋白 P 的作用及其关系，实验通过建立慢性不可预见性温和应激（Chronic Unpredictable Mild Stress ，CUMS）动物抑郁模型，同时海马内微量注射 TGF-β1以及 TGF-β1型受体激酶抑制剂 LY-364947，然后测量大鼠体重变化率，并通过糖水消耗以及旷场实验、悬尾实验检测大鼠行为变化，运用Elisa、Western blot分别检测大鼠海马组织内TGF-β1和硒蛋白P的含量变化。结果显示，与正常对照组相比，CUMS组大鼠表现出明显的抑郁样行为，海马组织内 TGF-β1含量升高，硒蛋白P表达下降；正常大鼠海马内注射 TGF-β1并不导致抑郁样行为，相反，CUMS同时海马内注射TGF-β1能逆转应激导致的抑郁样行为；正常和 CUMS大鼠海马注射 TGF-β1均能明显抑制硒蛋白P的表达；而应激的同时注射 TGF-β1型受体激酶抑制剂 LY-364947同样具有抗抑郁效应，此时硒蛋白P表达较CUMS组明显升高。以上结果表明：海马TGF-β1和硒蛋白P参与了应激性抑郁的发生；硒蛋白P对海马可能具有保护作用，TGF-β1通过 TGF-β1型受体抑制硒蛋白P表达可能是导致抑郁发生的途径之一，而 TGF-β1抗抑郁作用可能是

In order to investigate the role and relationship between transforming growth factor-beta1 (TGF-β1 )and selenoprotein P in depression induced by chronic unpredictable mild stress (CUMS),the effects of intrahippocampal microinjections of TGF-β1 and its receptor kinase inhibitor (LY-364947 ) on CUMS-induced depression and anxiety-like behaviors were investigated.The levels of depression like behaviors and related properties were measured using open-field test,tail suspension test,sucrose consumption and the body weight.The content level of TGF-β1 and the selenoprotein P were detected by Elisa and Western blot respectively.The results show that compared with control group,CUMS rats showed significant depression-like behaviors,lower levels of selenoprotein P and higher levels of TGF-β1 in the hippocampus.Microinj ection of recombined TGF-β1 didn′t result in increase of depressive-like behaviors;however,intrahippocampal inj ection of recombined TGF-β1 can effectively reduce

目的：初步探索醒脾解郁方对抑郁模型大鼠的抗抑郁行为和血清激素、神经递质变化的影响。方法：本实验将SD大鼠随机分为4组：正常组、模型对照组、舍曲林对照组、中药（石菖蒲、西洋参、郁金、熟地黄）组,采用21 d慢性不可预见性温和应激建立抑郁大鼠模型,以糖水偏爱和旷野试验移动距离评价各组大鼠抑郁行为,用ELISA法测定大鼠血清5-羟色胺、皮质酮含量,并比较醒脾解郁方对其影响的作用。结果：21 d慢性应激建立大鼠抑郁模型后,与正常组比较,模型组体重降低明显（P〈0.01）,糖水偏爱率、旷场试验移动距离显著下降（P〈0.01）,同时模型组血清皮质酮含量显著增加（P〈0.01）、5-HT明显降低（P〈0.01）;与模型组比较,中药组和舍曲林组均能显著改善大鼠抑郁行为（P〈0.05）,并且醒脾解郁方和舍曲林均对抑郁大鼠血清皮质酮、5-HT均有显著逆转作用（P〈0.05）。结论：醒脾解郁方具有抗抑郁作用,并与舍曲林效果相当,并能逆转抑郁模型大鼠血清皮质酮、5-HT的作用,这可能是其改善抑郁的作用机制。

Objective:To preliminarily explore the effect of Xingpijieyu decoction on depressive behavior and serum 5-HT and corticos-terone on depression model rats.Methods:SD rats were randomly divided into 4 groups:normal group,model control group,sertraline control group,and traditional Chinese medicine (stone calamus,American ginseng,radix curcumae,cultivated land)group.21 days chro-nic unpredictable mild stress was adopted to establish the rat model of depression,using sucrose preference and open-field test to evaluate depression of rats,and compare the change of 5-HT and corticosterone form every groups of rats by ELISA.Results:After 21 days of chro-nic stress depression rats model made,compared with normal group,weight,preference for sugar water rate and open-field total distance of the model group were significantly decreased (P <0.01),and serum corticosterone increased significantly (P <0.01),serum 5-HT sig-nificantly decreased (P <0.01);Compared with model group,sertraline gro