鞘内注射孤啡肽对大鼠足底注入蜜蜂毒诱致长时程自发痛、痛敏和炎症的不同效果

为进一步了解孤啡肽在脊髓水平是否具有抗伤害及抗炎作用,本实验在具有多种痛行为表现的蜜蜂毒模型上观察了鞘内注射孤啡肽对大鼠一侧后足底注入蜜蜂毒所诱致的同侧自发缩足反射、原发热和机械性痛敏以及注射部位炎症反应的影响,同时观察了新的高选择性孤啡肽受体拮抗剂CompB的作用.结果表明与生理盐水对照组比较,鞘内注射孤啡肽(3、10、30 nmol/10μl)对蜜蜂毒诱发的自发缩足反射次数的抑制作用随剂量提高而增大,抑制率分别为37±7,43±6and57±11%(三个剂量vs对照,P＜0.05);而对蜜蜂毒诱发的注射部位炎症反应(爪体积、爪背腹厚度和蛋白渗出的增加)无显著影响.CompB(30 nmo1)可完全翻转10 nmol孤啡肽对自发缩足反射的抑制作用.鞘内单次或重复注射孤啡肽(10 nmol/10μl)对蜜蜂毒诱致的原发性热和机械性痛敏的发生和维持均无作用.本实验结果提示,外源性孤啡肽在脊髓通过孤啡肽受体的介导产生一定的镇痛作用,但是它可能仅对持续性自发痛有抑制作用,而对热和机械性痛敏及炎症反应均无影响.     

肾素-血管紧张素系统在调节肾脏活动和慢性肾功能不全中的作用

一、肾内RAS的组成、生物学特征及肾内分布;(一)有关RAS的研究进展;(二)肾脏组织局部的RAS;(三)AngⅡ受体的亚型及其在肾内的分布;二、AngⅡ对肾脏血流动力学的影响;三、AngⅡ对肾脏的非血流动力学效应;(一)AngⅡ的促生长作用及促纤维生成效应;(二)AngⅡ作为促炎症因子的作用;四、有关RAS在肾功能不全中的临床研究     

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     

Flavone glucosides with immunomodulatory activity from the leaves of Pleioblastus amarus

Three flavone glucosides, pleiosides A-C, were isolated from the leaves of Pleioblastus amarus, along with two known flavones: tricin and tricetin 3,5-dimethoxy-7-O-β-d-glucopyranoside. Their structures were elucidated by extensive spectral studies. Pleiosides A-C were found to inhibit the proliferation of murine T and significantly stimulate the proliferation of murine B lymphocytes in vitro.     

Cloning and functional characterization of the human GLUT7 isoform SLC2A7 from the small intestine

Facilitated glucose transporters (GLUTs) mediate transport of sugars across cell membranes by using the chemical gradient of sugars as the driving force. Improved cloning techniques and database analyses have expanded this family of proteins to a total of 14 putative members. In this work a novel hexose transporter isoform, GLUT7, has been cloned from a human intestinal cDNA library by using a PCR-based strategy (GenBank accession no. AY571960). The encoded protein is comprised of 524 amino acid residues and shares 68% similarity and 53% identity with GLUT5, its most closely related isoform. When GLUT7 was expressed in Xenopus oocytes, it showed high-affinity transport for glucose (K(m) = 0.3 mM) and fructose (IC(50) = 0.060 mM). Galactose, 2-deoxy-d-glucose, and xylose were not transported. Uptake of 100 microM d-glucose was not inhibited by 200 microM phloretin or 100 microM cytochalasin B. Northern blotting indicated that the mRNA for GLUT7 is present in the human small intestine, colon, testis, and prostate. Western blotting and immunohistochemistry of rat tissues with an antibody raised against the predicted COOH-terminal sequence confirmed expression of the protein in the small intestine and indicated that the transporter is predominantly expressed in the enterocytes' brush-border membrane. The unusual substrate specificity and close sequence identity with GLUT5 suggest that GLUT7 represents an intermediate between class II GLUTs and the class I member GLUT2. Comparison between these proteins may provide key information as to the structural determinants for the recognition of fructose as a substrate.     

Participation of PI3K and ERK1/2 pathways are required for human brain vascular smooth muscle cell migration

Human brain vascular smooth muscle cell (HBVSMC) migration contributes to angiogenesis and several pathological processes in the brain. However, the molecular mechanism of angiogenesis, in which smooth muscle cell contributes, remains unclear. Our study investigates the role of vascular endothelial growth factor (VEGF) in the HBVSMC migration and elucidates the chemotactic signaling pathway mediating this action. We used the in vitro 'scratch' wound method to detect the HBVSMC migration. VEGF(165) (1-40ng/ml) induced the HBVSMC migration in a dose-dependent manner (P<0.05). VEGF(165) does not induce HBVSMC proliferation. Wortmannin, a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, significantly inhibited serine/threonine kinase Akt/protein kinase B (PKB) phosphorylation and reduced HBVSMC migration into the wound edge following VEGF(165) stimulation (P<0.05). PD98059, an extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor, also significantly inhibited ERK1/2 phosphorylation and reduced the numbers of SMC migration. Parallel distance measurement showed that VEGF(165) induced HBVSMC migration significantly reduced due to inhibition of PI3K or ERK1/2 phosphorylation (P<0.05). Our results demonstrate that VEGF(165) could induce HBVSMC migration but not proliferation in vitro. Inhibiting Akt/PKB or ERK1/2 phosphorylation could reduce VEGF(165) induced HBVSMC migration. We provide the first evidence that activation of PI3K or ERK1/2 pathways are a crucial event in VEGF(165) mediated signal transduction leading to HBVSMC migration.     

The discovery of 3-(N-alkyl)aminopropylphosphonic acids as potent S1P receptor agonists

3-(N-Alkyl)aminopropylphosphonic acids are potent agonists of four of the five known sphingosine-1-phosphate (S1P) receptor subtypes.     

Glyco-optimization of aminoglycosides: new aminoglycosides as novel anti-infective agents

Glyco-optimization (OPopS) of aminoglycosides has been performed by replacing the existing sugar moiety with a variety of sugar derivatives. Glycosylation of the 6-position of nebramine provided a library of novel 4,6-linked aminoglycosides (AMGs). Among them, compounds 8b,g,i,l, and 8u with 2"-amino, 2",3"-diamino, 2",4"-diamino, 3",4"-diamino, 3"-amino groups, respectively, showed significant antimicrobial activity against Gram-(+) and -(-) bacteria. Several were particularly potent against Pseudomonus aeruginosa with MICs in the 1-2 microg/mL range.