杜仲化学成分、药理作用和临床应用研究进展

杜仲Eucommia ulmoides是我国特有的珍稀濒危二类保护植物,其皮、叶、雄花和种子均具有药用价值和食用价值。化学成分研究发现杜仲不同部位（皮、叶、雄花、种子）主要有木脂素类、环烯醚萜类、黄酮类、苯丙素类、萜类和甾体类等成分,具有抗骨质疏松、抗炎、神经保护、降血压、降血糖、调血脂、免疫调节、抗菌、抗病毒等药理作用,广泛应用在医药、保健食品、饲料添加剂及日化用品等多个领域。通过对2000年1月—2022年12月在中国知网（CNKI）和PubMed数据库中发表的杜仲文献进行检索,共检索到相关文献1772篇,其中有效文献188篇。综述了杜仲在化学成分、药理作用、临床研究和开发应用方面的研究进展,为后续杜仲的临床应用及相关产品开发提供参考。     

硫酸镁减轻缺血再灌注性兔脑损伤作用的实验研究

目的 :探讨硫酸镁对缺血再灌注兔脑损伤的作用。方法 :15只兔随机均分至 :对照组、缺血组和缺血+硫酸镁处理组。阻断兔脑血管 6分钟 ,诱导全脑缺血。缺血再灌注 3天后 ,分别用HE染色和TUNEL染色 ,检测海马CA1 区神经元密度和凋亡神经元密度。结果 :缺血 +硫酸镁处理组海马CA1 区正常神经元密度为 140 .5 2±16 .2 3个 mm ,显著高于缺血组 (P <0 .0 1) ;缺血神经元密度为 2 4.18± 3 .16个 mm ,显著低于缺血组 (P <0 .0 1) ;凋亡神经元密度为 18.40± 8.0 8个 mm ,显著低于缺血组 (P <0 .0 1)。结论 :硫酸镁具有减轻兔缺血再灌注性全脑损伤的作用 ,其作用机制可能同抑制缺血后神经元凋亡有关     

Effects of ciliary neurotrophic factor on excitotoxicity and calcium-ionophore A23187-induced cell death in cultured embryonic striatal neurons

Ciliary neurotrophic factor (CNTF) has a protective effect on the striatum in animal models of Huntington's disease. However, the mechanism through which it exerts its effect is not clear. In this study, we show that there is a concentration-dependent direct protective effect of CNTF against N-methyl-D-aspartate-mediated excitotoxicity on striatal neurons in vitro. The CNTF has to be added more than half an hour before the insult for the effect to occur and its effect is eliminated by the presence of the protein synthesis inhibitor cycloheximide. This suggests that the protective mechanism of CNTF does not involve acute interference with the glutamate receptors, but probably requires gene/protein expression. We have also shown that the effect of CNTF against glutamate-induced excitotoxicity is dependent on the concentration of glutamate with a protective effect more evident at a low grade excitotoxic insult. Finally, we saw no effect of CNTF on calcium ionophore A23187-induced toxicity in striatal cultures, indicating that the growth factor does not promote survival by enhancing general defenses against raised intracellular levels of calcium.     

1-Aminoindan-1,5-dicarboxylic acid and (S)-(+)-2-(3'-carboxybicyclo[1.1.1] pentyl)-glycine, two mGlu1 receptor-preferring antagonists, reduce neuronal death in in vitro and in vivo models of cerebral ischaemia

Metabotropic glutamate (mGlu) receptors have been implicated in a number of physiological and pathological responses to glutamate, but the exact role of group I mGlu receptors in causing postischaemic injury is not yet clear. In this study, we examined whether the recently-characterized and relatively selective mGlu1 receptor antagonists 1-aminoindan-1,5-dicarboxylic acid (AIDA) and (S)-(+)-2-(3'-carboxybicyclo[1.1.1]pentyl)-glycine (CBPG) could reduce neuronal death in vitro, following oxygen-glucose deprivation (OGD) in murine cortical cell and rat organotypic hippocampal cultures, and in vivo, after global ischaemia in gerbils. When present in the incubation medium during the OGD insult and the subsequent 24 h recovery period, AIDA and CBPG significantly reduced neuronal death in vitro. The extent of protection was similar to that observed with the nonselective mGlu receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine [(+)MCPG] and with typical ionotropic glutamate (iGlu) receptor antagonists. Neuroprotection was also observed when AIDA or CBPG were added only after the OGD insult was terminated. Neuronal injury was not attenuated by the inactive isomer (-)MCPG, but was significantly enhanced by the nonselective mGlu receptor agonist (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic acid [(1S,3R)-ACPD] and the group I mGlu receptor agonist 3,5-dihydroxyphenylglycine (3,5-DHPG). The antagonists (+)MCPG, AIDA and CBPG were also neuroprotective in vivo, because i. c.v. administration reduced CA1 pyramidal cell degeneration examined 7 days following transient carotid occlusion in gerbils. Our results point to a role of mGlu1 receptors in the pathological mechanisms responsible for postischaemic neuronal death and propose a new target for neuroprotection.     

Synthesis of 3H and 14C labeled (S)‐3‐(5‐chloro‐2‐methoxyphenyl)‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐2H‐indol‐2‐one,maxipost™. An agent for post‐stroke neuroprotection

The syntheses of tritium labeled (S)‐3‐(5‐chloro‐2‐[OC³H₃]methoxyphenyl‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐1H‐indol‐2‐one, and carbon‐14 (S)‐3‐(5‐chloro‐2‐methoxyphenyl)‐1,3‐dihydro‐3‐fluoro‐6‐(trifluoromethyl)‐2H‐[2,3‐¹⁴C₂] indol‐2‐one are reported. The ³H‐labeled compound was prepared in a two‐step synthesis from C³H₃I. The final product was purified via chiral HPLC to yield the desired enantiomer in a 4% radiochemical yield and a specific activity of 60 Ci/mmol. The ¹⁴C‐labeled compound was prepared in a four‐step synthesis from diethyl [carboxylate‐¹⁴C₁,₂] oxalate. The final product was purified via chiral HPLC to yield the desired enantiomer in a 20% radiochemical yield and a specific activity of 28.4 μCi/mg. Copyright © 2002 John Wiley & Sons, Ltd.     

神经亲免素配体(NILs)的研究进展

介绍神经亲免素配体在设计、合成、构效关系以及促神经生长和神经保护研究方面的一些进展.     

急性缺血性卒中的神经保护药物研究进展

缺血性脑损伤的病理生理机制包括兴奋性氨基酸的释放、梗死灶周围去极化、炎症反应及神经元凋亡等。几乎对缺血级联反应的所有环节都已进行过神经保护药物的开发和试验。许多神经保护药物在脑缺血动物模型研究中证明有效,但临床试验效果却难以令人满意。本文就目前各类神经保护药治疗脑缺血的临床前期和临床试验的结果与进展作简要的回顾和展望。     

兴奋性氨基酸与青光眼

近年来随着对青光眼性视神经病变机制的深入研究,已证实兴奋性氨基酸与青光眼视网膜神经节细胞凋亡密切相关。21世纪青光眼的治疗模式正从传统的单纯降眼压向降眼压的同时从其他途径进一步加强神经保护转变,基础实验及部分临床研究证实干扰兴奋性氨基酸产生神经毒性的各环节均对神经元有保护作用,由此可以推测通过对兴奋性氨基酸的研究有望实现青光眼治疗史上的重大突破。     

灯盏细辛对NMDA所致的大鼠视网膜神经元损伤的保护作用

目的:探讨灯盏细辛(EBHM)是否对N-甲基-D天门冬氨酸(NMDA)导致的大鼠视网膜神经节细胞层(RGCL)神经元兴奋毒性损伤有保护作用。方法:60只健康SD大鼠随机分为4组,其中6只为正常对照组(A组),其余54只随机分为3组,分别为B组(EBHM组),C组(生理盐水加NMDA组),D组(EBHM加NMDA组),每组各18只大鼠。C、D两组大鼠右眼玻璃体内注射NMDA 10 nmol/2 μl制成视网膜损伤模型,左眼玻璃体内注射相同剂量PBS液作为自身对照。B组及D组均在NMDA注射前7d起按15 mg·100 g-1·d-1剂量予6％EBHM腹腔内注射,C组予生理盐水0.5 ml腹腔内注射。在NMDA处理后4,7和14 d处死动物剥取视网膜作全层铺片行RGCL神经元计数分析。结果:正常对照组双眼RGCL神经元计数比较差异无显著性意义(P=0.200)。NMDA干预后4、7 d和14 dEBHM组RGCL神经元计数,双眼与正常对照组比较差异无显著性意义(P>0.05)。生理盐水加NMDA及EBHM加NMDA组实验眼在以上各时段RGCL神经元计数与正常比较差异均有非常显著性意义(P<0.001),左眼与正常对照组比较差异无显著性意义(P>0.05)。实验眼14 d时RGCL神经元计数EBHM加NMDA组高于生理盐水加NMDA组,两者比较差异有显著性(P=0.044),但仍低于正常对照组(P<0.05)。结论:单独使用EBHM对正常大鼠RGCL神经元计数无影响,EBHM可对N     

热休克蛋白27在实验性青光眼中表达的研究

目的　观察大鼠眼压升高后热休克蛋白 2 7(HSP2 7)在视网膜中的表达。方法　5 0只Wistar大鼠随机分为高眼压组和sham对照 (假手术 )组。采用电凝鼠巩膜表面至少3组静脉及角膜缘周围血管 ,减少房水静脉回流升高眼压。观察手术后 1、2、3、4及 8周大鼠眼压 ,同时免疫组化检测视网膜中HSP2 7的表达及分布情况。结果　高眼压组右眼术后眼压明显升高。术后 1周眼压 :(30 .12± 5 .18)mmHg(1kPa =7.5mmHg) ,1周后眼压基本稳定。术后各时间点高眼压组右眼眼压与术前、左眼及sham对照组右、左眼间比较 ,差异有显著性 (P <0 .0 0 1)。视网膜中HSP2 7阳性表达主要表现在视网膜神经节细胞的胞浆内及神经纤维层中 ,HSP2 7阳性表达率在术后 1、2、3、4及 8周 ,高眼压组右眼与左眼、sham对照组右、左眼间比较 ,差异有显著性 (P <0 .0 0 1) ,同时发现视网膜中HSP2 7阳性表达随着眼压升高及高眼压持续时间延长逐渐增强。结论　内源性HSP2 7在青光眼视网膜神经节细胞中表达增强可能在青光眼视神经保护中具有重要作用。