脑室注射r-氨基丁酸(GABA)对大鼠垂体-甲状腺分泌功能的抑制效应

脑室注射10μl含8molGABA的人工脑脊液后60min,大鼠血清TSH、T4、T3含量与注射人工脑脊液的对照组比显著降低(P<0.001、0.01、0.05);若在注射GABA前1min,预先注射10μl多巴胺受体阻断剂氟哌啶醇(5g/1)、10μl肾上腺素受体阻断剂酚妥拉明(10g/1)或10μlGABA受体阻断剂青霉素(3.35×10~(-2)mol/l),可以阻断GABA对TSH、T4、T3分泌的抑制效应.结果证明脑中GABA能系统参与垂体-甲状腺功能的调制,提示GABA通过多巴胺能和肾上腺素能神经元,抑制下丘脑分泌TRH,从而影响垂体分泌TSH,最终抑制了甲状腺的分泌功能.     

Toll样受体信号通路的3条途径在大鼠肝再生中抑制库普弗细胞免疫反应

为从基因转录水平了解大鼠肝再生中Toll样受体信号通路调节库普弗细胞免疫反应的途径和方式,首先建立大鼠2/3肝切除(partial hepatectomy,PH)模型,从中分离库普弗细胞进行基因微阵列分析.发现Toll样受体信号通路的23个基因及其调节免疫反应的62个基因与大鼠肝再生相关.基因协同作用(Ep(t)值)和同类提取法分析表明,大鼠肝再生进展阶段,Toll样受体信号通路通过TLR/NF-κB,TLR/MAPK,TLR/IRF等3条途径和TLR4,MAL,UNC93B1,AP1S2,IRF1等5个关键基因抑制库普弗细胞免疫反应.     

慢性应激性抑郁发生中海马糖皮质激素对BDNF的影响

为证明慢性应激性抑郁的发生与应激引起的糖皮质激素(Glucocorticoids,GCs)分泌增加,导致海马脑源性神经营养因子(Brain Derived Neurothrophic Factor,BDNF)表达抑制有关.实验用大鼠通过建立慢性不可预见性温和应激(Chronic Unpredictable Mild Stress,CUMS)抑郁模型,通过海马微量注射皮质酮及糖皮质激素受体拮抗剂米司非酮,然后测量体重,观测行为学表现,并用酶联免疫吸附法检测海马内GCs和BNDF含量.结果显示:CUMS明显诱发大鼠抑郁样行为,海马组织中皮质酮明显升高,BDNF水平明显下降.海马微量注射米司非酮,使CUMS诱发的大鼠抑郁样行为明显改善,且BDNF水平明显升高.正常大鼠海马微量注射皮质酮后,表现出与CUMS组相似的抑郁样行为,且海马组织中BDNF明显下降.以上结果表明,慢性应激引起大鼠海马皮质酮明显升高,使海马BDNF表达明显减少,导致抑郁发生.糖皮质激素Ⅱ型受体(Glucocorticoids Receptor,GR)起着重要作用.     

顺序注射-电化学发光体系研究茶多酚的抗氧化性

茶多酚是茶叶中酚类及其衍生物的总称,具有重要的保健功能和药用价值,研究茶多酚的抗氧化能力和自由基清除能力对阐释茶多酚的生理活性具有重要的理论意义.本实验构建了新型的顺序注射电化学发光系统,在该系统内,利用碱性条件下茶多酚对鲁米诺-H2O2电化学发光行为的抑制作用,建立了抗氧化性能研究的顺序注射电化学发光分析新方法,此方法具有操作简单、快捷,灵敏度高等优点.在最优条件下,测得茶多酚的IC50为14 mg/L,且发光值的降低程度与茶多酚浓度在2.5-25 mg/L范围内呈现良好的线性关系,回归方程为Y=2.774X＋10.06（r=0.990 9）.实验结果为评价抗氧化剂清除自由基的能力提供了新的技术手段.     

橙皮素对血管内皮细胞NO分泌功能的影响

考察了橙皮素对人脐静脉内皮细胞(HUVECs)NO分泌功能的影响,探讨其作用机制.为此采用DAN法测定HUVECs分泌NO的水平,用人乳腺癌MCF-7细胞(雌激素受体阳性)促增殖实验和报告基因模型实验评价橙皮素的雌激素样活性.结果显示在内源雌激素水平较低的条件下,橙皮素在12.5～100 μmoL/L浓度范围内,能够促进HUVECs分泌NO,并呈剂量依赖性.此作用能够被雌激素受体拮抗剂ICI182,780和放线菌素D阻断.橙皮素与E2同时作用时,HUVECs分泌NO水平较两者单独作用时显著下降.而在内源雌激素水平较高的条件下,橙皮素抑制HUVECs分泌NO.橙皮素能够促进MCF-7细胞增殖,并且能够被ICI182,780完全阻断,同时,橙皮素能够部分拮抗E2对MCF-7细胞的促增殖作用.另外,橙皮素能够诱导ERα控制的报告基因表达.从而可认为橙皮素属于雌激素受体部分激动剂,对血管内皮细胞NO分泌功能具有调节作用,其机理涉及雌激素受体信号途径和基因转录调节.     

SKF83959调节大鼠的自发活动和焦虑行为

为了探讨多巴胺D1类受体激动剂SKF83959在动物自发活动、焦虑情绪和学习记忆方面的作用,将3月龄雄性大鼠随机分为给药组和空白对照组,分别腹腔注射1.0mg/kgSKF83959或等体积PBS缓冲液后,进行行为学测试.实验结果显示,与对照组相比,SKF83959注射后的大鼠在开放场测试中水平方向活动次数和总活动时间显著增加;在高架十字迷宫中给药组大鼠在闭臂区的停留时间更长,总穿臂次数和开臂、闭臂进臂次数也都减少.在恐惧性条件学习中,SKF83959处理组大鼠的记忆能力与对照组大鼠之间没有明显差异.结果提示,SKF83959能够提高大鼠的活动量,增加大鼠的焦虑情绪行为,而对大鼠恐惧记忆没有明显影响.     

肿瘤坏死因子受体相关因子2(TRAF2)在TNF信号传导中的作用

肿瘤坏死因子受体相关因子(TRAFs)是经TNF受体超家族和IL-1R/TLR超家族信号传导通路的重要成分.TNF信号传导中,TRAF2作为接头蛋白和调控因子在几乎所有分支通路中起作用,在调节TNF-R1介导的NF-κB和JNK激活过程中起重要作用.近来的研究提示,TRAF2是凋亡信号传导和抗凋亡信号传导的分支点.本文主要阐述TRAF2的分子结构及它的结构与功能的关系,TNF信号传导的分子机制及TRAF2在其中的作用,重点关注TRAF2作为凋亡途径和NF-κB介导的存活途径,即这2条相互拮抗的信号传导途径的分支点的重要性.     

维药异常黑胆质成熟剂对乳腺增生模型大鼠乳腺组织病理形态及血清性激素水平的影响

 为探讨维药异常黑胆质成熟剂对乳腺增生模型大鼠的治疗作用及可能的作用机制,选用清洁级雌性Wistar 大鼠60 只,随机分为6 组：正常对照组、模型组、阳性对照组（三苯氧胺组）、异常黑胆质成熟剂高、中、低剂量组,采用大鼠右下肢肌肉注射雌、孕激素建立乳腺增生病模型,进行药物干预（三苯氧胺1.8 mg/kg,胆质成熟剂高、中、低剂量分别为3.75、7.5、15 g/kg）。运用光学显微镜观察维药异常黑胆质成熟剂对实验性乳腺增生症大鼠乳腺形态学的影响,放射免疫测定法检测其血清激素水平。结果表明,异常黑胆质成熟剂能减轻上皮细胞、间质纤维组织增生程度,改善模型大鼠乳腺组织病理形态学改变,调节血清激素水平,降低血清雌二醇（E₂）、黄体生成素（LH）、升高孕酮（P）、睾酮（T）、催乳素（PRL）及卵泡刺激素（FSH）水平,与模型组比较具有统计学差异（P<0.01 或P<0.05）。由此可见,异常黑胆质成熟剂对乳腺增生症大鼠的乳腺组织形态改变有一定的修复作用,同时能够降低大鼠血清雌激素水平,显著提高孕激素水平,且雌、孕激素比例失调状态也能够得到改善。     

乙酰胆碱对非洲爪蟾卵母细胞ATP-激活电流的调制作用

研究乙酰胆碱对爪蟾卵母细胞上ATP激活电流的影响及其机理.用双电极电压钳技术记录爪蟾卵母细胞的细胞外液加入乙酰胆碱对ATP激活电流（IATP）的影响.结果显示,乙酰胆碱对大多数细胞IATP具有增强作用,而对少数细胞IATP具有抑制作用,且均呈现浓度依赖性;乙酰胆碱对IATP的调制作用是通过毒蕈碱样乙酰胆碱受体（M受体）激活实现的.     

杏仁核注射5-HT对慢性应激抑郁大鼠胃运动的影响

运用慢性不可预见性温和应激建立抑郁模型,通过体重变化率、糖水偏好、敞箱等实验方法观察大鼠行为表现及胃运动,探讨慢性应激性抑郁大鼠胃活动的变化及杏仁核注射5-HT对慢性不可预见性应激引起的胃活动变化的影响.结果显示,慢性不可预见性应激引起大鼠体重呈负增长,糖水偏好率、敞箱实验评分显著降低;应激大鼠平均胃内压及胃收缩幅度也显著降低;杏仁核注射5-HT能明显改变应激性抑郁导致的胃活动减弱,5-HT1A受体阻断剂能明显影响5-HT的作用;切断双侧膈下迷走神经,杏仁核注射5-HT增强胃运动的效应被消除.以上结果说明,慢性不可预见性应激性抑郁可导致胃运动减弱,杏仁核注射5-HT可加强抑郁状态下胃运动,而5-HT的这种效应部分是由1A型受体介导,经迷走神经传出.     

Identification of receptors for neuromedin U and its role in feeding

Neuromedin U (NMU) is a neuropeptide with potent activity on smooth muscle which was isolated first from porcine spinal cord and later from other species. It is widely distributed in the gut and central nervous system. Peripheral activities of NMU include stimulation of smooth muscle, increase of blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. An NMU receptor has not been molecularly identified. Here we show that the previously described orphan G-protein-coupled receptor FM-3 (ref. 15) and a newly discovered one (FM-4) are cognate receptors for NMU. FM-3, designated NMU1R, is abundantly expressed in peripheral tissues whereas FM-4, designated NMU2R, is expressed in specific regions of the brain. NMU is expressed in the ventromedial hypothalamus in the rat brain, and its level is significantly reduced following fasting. Intracerebroventricular administration of NMU markedly suppresses food intake in rats. These findings provide a molecular basis for the biochemical activities of NMU and may indicate that NMU is involved in the central control of feeding.     

Frizzled regulation of Notch signalling polarizes cell fate in the Drosophila eye

The Drosophila eye, a paradigm for epithelial organization, is highly polarized with mirror-image symmetry about the equator. The R3 and R4 photoreceptors in each ommatidium are vital in this polarity; they adopt asymmetrical positions in adult ommatidia and are the site of action for several essential genes. Two such genes are frizzled (fz) and dishevelled (dsh), the products of which are components of a signalling pathway required in R3, and which are thought to be activated by a diffusible signal. Here we show that the transmembrane receptor Notch is required downstream of dsh in R3/R4 for them to adopt distinct fates. By using an enhancer for the Notch target gene Enhancer of split mdelta, we show that Notch becomes activated specifically in R4. We propose that Fz/Dsh promotes activity of the Notch ligand Delta and inhibits Notch receptor activity in R3, creating a difference in Notch signalling capacity between R3 and R4. Subsequent feedback in the Notch pathway ensures that this difference becomes amplified. This interplay between Fz/Dsh and Notch indicates that polarity is established through local comparisons between two cells and explains how a signal from one position (for example, the equator in the eye) could be interpreted by all ommatidia in the field.     

Exendin 4高活性短肽模拟物的筛选及生物活性#br#

以细胞表面胰高血糖素样肽(GLP-1)受体为靶标, 利用噬菌体筛选技术, 通过Exendin-4竞争性洗脱筛选GLP-1受体激动剂, 得到了12肽模拟物EPA. 细胞增殖实验结果表明： EPA和Exendin-4均可促进胰岛β细胞增殖活性, 在40~200 μmol/L内, EPA比Exendin-4的活性高5%~25%; 在100 mmol/L高浓度葡萄糖毒性下, EPA通过抑制bax基因和上调bcl 2基因表达及抑制Caspase 3活性来抑制胰岛β细胞的凋亡; EPA是具有高活性的Exendin-4短肽模拟物, 可通过bcl-2/bax…Caspase 3信号通路抑制线粒体的凋亡.     

Transient expression of IL-2 receptor precedes the differentiation of immature thymocytes

The growth of mature T lymphocytes after activation by antigen is regulated by the binding and endocytosis of interleukin-2 (IL-2). In the thymus, approximately 50% of adult thymocytes that carry neither the CD4 nor the CD8 antigen and day 14-15 fetal CD4-8- thymocytes express receptors for IL-2(IL-2R). The CD4-8- (double-negative) subpopulation of thymocytes contains the precursors of cells that can differentiate along an unknown pathway into thymocytes bearing either CD8 or CD4, with the characteristics of mature T lymphocytes. The basis for IL-2R expression by double-negative thymocytes is unclear as they appear to lack a functional T-cell receptor/CD3 complex through which activation of peripheral T cells is mediated. The argument for a role for IL-2 in thymocyte differentiation has also been complicated by conflicting reports on the inability or capability of double-negative thymocytes to respond to IL-2 in vitro. At present, both the nature of the stimuli within the thymic micro-environment which induce IL-2R expression and its relevance to thymocyte differentiation are not known. We show here that the IL-2R-bearing subset has a greater potential to differentiate into phenotypically mature T lymphocytes than do IL-2R-negative thymocytes. In addition, progeny of IL-2R-negative donor cells transiently express IL-2R in the thymuses of adoptive hosts before generating CD8 and/or CD4-positive thymocytes. These results identify the IL-2R-positive cells as a more differentiated double-negative thymocyte subset on the pathway to mature T lymphocytes.     

胃癌组织中环氧化酶-2和血管内皮生长因子-C、D、R3 mRNA表达的研究

目的:环氧化酶-2(COX-2)、血管内皮生长因子(VEGF)-C、D及其受体3(R3)与肿瘤关系密切.研究COX-2和VEGF-C、D、R3在胃癌中的表达,探讨其在胃癌淋巴管生成和转移中的作用及其相关性.方法:采用RT-PCR方法,对22例胃癌及癌旁组织手术标本中COX-2和VEGF-C、D、R3mRNA的表达进行半定量研究.结果:胃癌组织中COX-2和VEGF-C、VEGF-R3mRNA表达均高于相应的癌旁非癌组织(P<0.05),其中COX-2和VEGF-C在淋巴结转移组中的表达均高于非淋巴结转移组(P<0.05),且COX-2和VEGF-C mRNA表达间存在明显相关性(P<0.05).结论:胃癌组织中有COX-2和VEGF-C、D、R3的高表达,而COX-2可能参与VEGF-C、D和/或R3淋巴管生成通路,其表达可能在胃癌淋巴管浸润和转移过程中发挥着重要作用.     

植物光合羧化酶活力比的简捷测定法及其在鉴定牧草光合类型上的应用

本文建立了一种测定植物 RuBPCase 和 PEPCase 活力比的既准确又简捷的方法,从而使以两种羧化酶活力比值(R/P)为指标鉴定植物光合类型的想法交得切实可行。通过对10种已知光合类型植物的测定,证明 R/P 值是鉴定光合途径的可靠指标。R/P>1为 C3植物,R/P<1为 C4植物。最后以 R/P 为指标对10种习见牧草的光合类型进行了首次鉴定。     

Signal transduction pathways mediated by colony stimulating factor-1 receptor

Colony-stimulating factor-1 (CSF-1), which is necessary for cell proliferation and differentiation, regulates both immediate and delayed early responses throughout G1 phase. The binding of CSF-1 to its receptor (CSF-1R) triggers phosphorylation of the receptor and its intrinsic tyrosine kinase. The activated receptor binds directly to cytoplasmic effector proteins, which induce multiple-signal transduction pathways. CSF-1 can induce the c-myc gene expression via Ras and Ets-related proteins. The expression of c-fos/jun family genes is also targeted following the activation of Ras. CSF-1R activates STAT1 and STAT3 to participate in signaling, but JAKs do not appear to contribute to signaling by CSF-1R. CSF-1R activates PI3-kinase, and PI3-ki can interact with downstream proteins by the MAPKK-related pathway independent of Ras/Raf. PC-PLC can enforce signaling in response to CSF-1. Furthermore, the turnover and dephosphorylation by the phosphatase SHPTP1 of CSF-1R are the major mechanism in the negative regulation of signaling by CSF-1R     

Uranyl-HTTDN与R/S-丙硫磷农药的配位及选择性

为了探讨新型铀酰受体对丙硫磷的对映选择性,设计了一种新颖的配体:2-(2-羟基-3-甲氧基苯基)-9-(2-羟基苯基)硫代吡喃并[3,2-h]硫代色烯-4,7-二酮(HTTDN),并将HTTDN与铀酰离子结合,来构建一个新的Uranyl-HTTDN受体。在本工作中,利用密度泛函理论研究了Uranyl-HTTDN对R/S-丙硫磷农药的对映选择性识别。结果表明,在真空和甲苯中,Uranyl-HTTDN可以通过与丙硫磷中的S₃原子配位来有效的识别R/S-丙硫磷,选择性系数均大于90%。