Ca2+在链霉素对大鼠颈动脉窦压力感受器反射影响中的作用

在23只隔离灌流颈动脉窦区的麻醉大鼠上, 观察了链霉素(streptomycin, SM)对动脉压力感受器反射影响的离子机制.结果: (1) 用SM (200 μmol/L)隔离灌流大鼠颈动脉窦区时, 压力感受器机能曲线向右上方移位, 曲线最大斜率及反射性血压下降幅度均减小(P<0.01), 提示SM对压力感受器反射有抑制作用; (2)预先灌流高Ca2+溶液(4 mmol/L)后, 可部分消除SM (200 μmol/L)对压力感受器反射的抑制作用(P<0.01), 使其压力感受器机能曲线向左下方移位, 曲线的最大斜率由0.27±0.04增至0.37±0.02 (P<0.01), 反射性血压下降幅度由4.32±0.14 kPa增至6.18±0.17 kPa (P<0.01), 而阈压和饱和压则分别从10.29±0.29和27.26±0.42 kPa降至9.98±0.33 和25.22±0.38 kPa (P<0.05); (3) 用Ca2+通道激动剂Bay K 8644 (500 nmol/L)预处理, 可完全消除SM (200 μmol/L)对压力感受器反射的抑制效应; (4)预先给予Ca2+激活性K+通道阻断剂(charybdotoxin, ChTX, 100 nmol/L), 对压力感受器反射无明显影响, 加入SM后仍呈现抑制作用.以上结果表明, SM可能是通过抑制颈动脉窦压力感受器中机械敏感性通道的Ca2+内流而发挥作用.     

Pioglitazone suppresses advanced glycation end product-induced expression of plasminogen activator inhibitor-1 in vascular smooth muscle cells

Advanced glycation end products (AGEs) play an important role in vascular complications of diabetes, including fibrinolytic abnormalities.Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARΥ) agonist, has recently been shown to reduce circulating plasminogen activator inhibitor-1 (PAI-1) levels in diabetes mellitus. In the present study, we investigated the effects of pioglitazone on the expression of local PAI-1 in rat vascular smooth muscle cells (VSMCs) induced by AGEs and the underlying mechanism. The result showed that AGEs could enhance the PAI-1 expression by 5.1-fold in mRNA and 2.7-fold in protein level, as evaluated by real-time RT-PCR and Western blotting,respectively. Pioglitazone was found to down-regulate the AGE-stimulated PAI-1 expression in VSMCs. However, these inhibitory effects were partially attenuated by the PPARΥ antagonist, GW9662. Furthermore, we found that AGEs induced a rapid increase in phosphorylation and activation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2). The ERK kinase inhibitor, UO126, partially prevented the induction of PAI-1 by AGEs. Moreover, pioglitazone was also found to inhibit the phosphorylation of ERKi/2. Taken together, it was concluded that pioglitazone could inhibit AGE-induced PAI-1 expression, which was mediated by the ERK1/2 and PPARΥ pathways. Our findings suggestedpioglitazone had a therapeutic potential in improving fibrinolytic activity, and consequently preventing thromboembolic complications of diabetes and cardiovascular disease.     

基于GABA A受体评估双氟沙星对异育银鲫的安全性

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雌激素信号通路概述

过去几十年,人们一直认为雌激素信号通路是雌激素与细胞核中的雌激素受体(ER)结合,作用于雌激素受体反应元件调节基因表达,从而改变细胞功能。雌激素不但与核ER结合,也能与膜ER结合激活PI3K信号通路。G蛋白偶联受体(GPR30)也能与雌激素结合,激活PI3K信号通路。雌激素通过结合不同雌激素受体改变细胞生理功能。我们对雌激素信号通路做简要综述。     

代谢型谷氨酸受体在突触可塑性中的作用研究进展

突触可塑性是近 30年来神经科学领域的研究热点之一 ,它主要包括长时程增强 (long termpotentiation ,LTP)和长时程抑制 (long termdepression ,LTD)。以往的研究已经证实 ,离子型谷氨酸受体 (iGluRs)中的NMDA受体和AMPA受体 ,在LTP和LTD的诱导和维持中通过阳离子内流 ,引起细胞内的级联反应而起作用。新近的研究发现 ,代谢型谷氨酸受体 (mGluRs)与G蛋白偶联 ,通过细胞内的多种信使系统介导慢突触传递。本文主要就mGluRs在不同脑区LTP和LTD中的作用进行综述     

Fractalkine及其受体CX3CR1与神经病理性疼痛

神经病理性疼痛是由于神经系统的损伤和炎症引起的,发病率日益增高,但是根本机制仍然不清楚。动物实验表明细胞因子和趋化因子参与神经病理性疼痛的发生。作为唯一的CX3C亚族的膜结合型趋化因子Fractalkine（Fkn）在神经病理性疼痛发病机制中的作用日益受到关注,有望成为神经病理性疼痛治疗的新靶点。Fkn及其受体有其特殊结构和功能作用,本文就其参与神经病理性疼痛的可能机制,调节吗啡的效应作一综述。     

重症肌无力小鼠模型的建立

目的建立重症肌无力小鼠模型。方法电鳗乙酰胆碱受体(TnAChR)和完全弗氏佐剂(CFA)混合物免疫C57BL/6J小鼠,经二次加强免疫后,检测肌力、腓肠肌肌电图、膈肌终板电镜、血清抗体水平等指标。结果与对照小鼠相比,发病小鼠表现出肌力减弱的症状,肌电图显示小鼠腓肠肌复合动作电位振幅幅度显著下降,电镜证实神经肌接头处突触后膜变平、皱褶减少、空泡样变性,发病小鼠血清抗体水平明显升高。结论成功建立了重症肌无力小鼠模型,有助于探讨其发病机理及探索治疗自身免疫病新的途径和方法。     

胃泌素及其受体的分子生物学研究进展

胃泌素是一种刺激胃酸分泌的胃肠道激素,并能刺激胃肠道粘膜及肿瘤的生长。胃泌素曾被认为是一种自泌生物因子在胃肠道恶性肿瘤中起作用,但是近年来人们更加重视胃泌素原,甘氨酸胃泌素及其受体在恶性肿瘤中的作用。     

Toll样受体3抑制人类巨噬细胞感染HIV的机制研究

Toll样受体（Toll like receptor,TLR）是固有免疫系统中的病原模式识别受体,在巨噬细胞抗感染免疫中发挥重要作用。TLR3特异性识别双链RNA,诱导细胞内多重信号传导,引发巨噬细胞产生抗病毒活性。本研究以TLR3激活剂多聚次黄苷酸-胞苷酸（polyinosinie：polycytidylic acid,Polyl：C）刺激人类巨噬细胞,发现能显著抑制胞内HIV病毒感染和复制。Poly I：C刺激后,巨噬细胞I型干扰素（interferon,IFN）和抗HIV胞嘧啶脱氨酶（APOBEC3G,A3G）表达水平显著上调;且具有抗HIV作用的MicroRNA（miRNA-28,125b,150,223,and382）的表达也显著上调。本研究初步揭示了TLR3激活后抗HIV感染的机制。     

NMDA受体在海马CA3区习得性TP保持中的作用

The effect of microinjection of 2-amino-5-phosphonovaleric acid (APV), a selective NMDA receptor antagonist, into the rat hippocampal CA3 area on the synaptic efficacy and related conditioned behavior during the acquisition and consolidation of discrimination learning behavior was examined. The results showed: (1) After population spike (PS) amplitude had just increased to the maximum through training i.e. learning-dependent LTP had just formed, APV 1 microliter (2 mmol/L) was injected into CA3 area, then the rats were trained during the time of efficacy of the drug in every experimental block. The result demonstrated that the PS amplitude could not be maintained at the highest level but decreased to the pre-experiment level after 8 blocks. Correct response percentage of rats could not be consolidated with further training but decreased to less than 10%. (2) After the PS amplitude had kept up at the highest level, APV 1 microliter (2 mmol/L) was injected into CA3 area, then the rats were trained during the time of efficacy of the drug in every experimental block, in which case the PS amplitude also could not be maintained at the highest level but decreased to the pre-experiment level after 14 blocks. Correlatively, when the correct response percentage of rats decreased gradually to less than 10%, the conditioned response of the animals extinguished, but its extinction speed was slower than it was in result (1). These results suggest that the NMDA receptor in CA3 area plays an important role in the maintenance of the learning-dependent long-term potentiation.