小檗碱对糖尿病肾病大鼠肾小球系膜细胞增殖和分泌TGF-β1的影响

目的 探讨小檗碱对糖尿病肾病大鼠肾小球系膜细胞增殖和分泌TGF-β1的影响.方法 分离培养糖尿病肾病大鼠肾小球系膜细胞,用MTT法检测系膜细胞的增殖能力,ELISA法测定系膜细胞分泌的TGF-β1,放射免疫法测定系膜细胞产生cAMP水平.结果 间接免疫荧光鉴定结果显示所培养的细胞为系膜细胞.小檗碱(15、30、60、120 μmol/L)能有效的抑制糖尿病肾病大鼠系膜细胞的增殖和TGF-β1的分泌,并显著升高糖尿病肾病大鼠系膜细胞的cAMP水平.结论 升高糖尿病肾病大鼠系膜细胞cAMP水平可能是小檗碱发挥抑制系膜细胞过度增殖和分泌的机制之一.     

从“阳化气,阴成形”角度阐释肠促胰素在糖脂代谢中的作用

糖脂代谢是人体生命活动中重要的物质代谢过程,其合成代谢与分解代谢的相互协调确保正常的生理功能。阴阳学说中“阳化气”“阴成形”的理论是对机体生命规律及物质与能量关系的生动描述。抑胃肽(GIP)和胰高血糖素样肽1(GLP-1)作为2种主要的肠促胰素,由肠道内分泌细胞产生,作用于胰腺、脑、肝脏等组织,合成与分解饮食中的糖类与脂质,为机体提供能量并存储能量。其中,GIP刺激白色脂肪,促进脂质储存,具有类似于“阴成形”的作用,GLP-1刺激棕色脂肪,增加产热,具有类似于“阳化气”的作用,二者之间还有对立制约、互根互用、消长平衡的阴阳关系。GIP与GLP-1的关系与机体糖脂代谢的生理、病理学密切相关。糖脂代谢紊乱早期均以瘀滞状态为主,糖尿病以阳盛阴病为主,而肥胖症以阴盛阳病为主。调整阴阳可改善糖脂代谢紊乱状态,现代医学研究表明,共同激动GIP与GLP-1,会产生更好地控制血糖、体质量的效果。本文借助中医阴阳理论,以肠促胰素为切入点,浅析GIP与GLP-1在糖脂代谢中的作用关系,以丰富中医药对糖尿病、肥胖症等代谢疾病的研究思路。     

Mecanismos moleculares de los efectos benéficos de la alicina sobre la enfermedad cardiovascular

Cardiovascular diseases (CVD) include a group of diseases whose common denominator is the affection of the blood vessels, heart, and heart rate. The treatment of CVD represents high costs to the health systems and is focused on the control of risk factors. Despite the existence of a great variety of treatments of the CVD, these continue as the main cause of mortality mainly due to the multifactorial origin, and therefore more than one drug is required. In this context, allicin, a compound derived from garlic, has shown regulate the expression of signaling pathways and risk factors associated with the progression of CVD. Therefore, the objective of this work is to review the cellular and molecular mechanisms through which allicin exert its therapeutic effects and to describe the scientific evidences why allicin represents a potential candidate to assist in the treatment of CVD.     

The Role of Resveratrol in Eye Diseases—A Review of the Literature

Resveratrol (3,5,4′-trans-trihydroxystilbene) is a polyphenolic phytoalexin belonging to the stilbene family. It is commonly found in grape skins and seeds, as well as other plant-based foods. Oxidative stress and inflammation play a key role in the initiation and progression of age-related eye disorders (glaucoma, cataracts, diabetic retinopathy, and macular degeneration) that lead to a progressive loss of vision and blindness. Even though the way resveratrol affects the human body and the course of many diseases is still the subject of ongoing scientific research, it has been shown that the broad spectrum of anti-inflammatory and neuroprotective properties of resveratrol has a beneficial effect on eye tissues. In our research, we decided to analyze the current scientific literature on resveratrol, its possible mechanisms of action, and its therapeutic application in order to assess its effectiveness in eye diseases.     

基于分子水平的AD治疗药物作用机制研究进展

目的通过总结Alzheimer’s disease(AD)的致病机制,探讨目前临床上抗AD药物的研究进展情况,为临床合理用药及相关创新药物的研发提供参考和思路。方法通过查阅国内外相关文献,整理、分析、归纳AD的最新研究进展和药物治疗情况。结果 AD由于病因、致病机制复杂,导致其致病机制假说众多,目前市场上的治疗药物大多是针对单一致病机制而研制的,没有考虑到疾病不同时间、阶段、个体差异等因素对治疗药物的要求,导致了大多数药物在AD治疗时具有一定的局限性,并且由于某些药物的毒副作用,这就给临床合理用药带来了诸多困难。结论中药由于其在AD治疗上表现出的独特的治疗效果,受到越来越多学者的重视,其中中药单体成分在AD治疗方面的研究已经较为完善,但是中药复方、复方多成分之间相互作用及对分子机制相关性影响的研究还较少,因此我们应加强药物多成分之间药效及机制相关性的研究,为更好地、有效地、快捷地开发创新药物提供文献依据。     

三氧化二砷对实验性小鼠支气管哮喘气道重塑及TGF-β1、VEGF表达的影响

目的探讨三氧化二砷（As2O3）对支气管哮喘气道重塑的影响。方法将实验BALB/c小鼠40只随机分为正常对照组、模型组、地塞米松治疗组和As2O3治疗组,模型组通过腹腔注射卵白蛋白（OVA）致敏及反复雾化OVA吸入激发8周,建立支气管哮喘气道重塑动物模型,地塞米松和As2O3治疗组每次雾化吸入前分别给予地塞米松2 mg/kg和As2O34 mg/kg腹腔内注射。应用HE染色,观察支气管、肺组织的病理形态改变,应用图像分析系统测定气道重塑指标,应用免疫组化法检测各组小鼠肺组织中的转化生长因子β1（TGF-β1）、血管内皮生长因子（VEGF）的蛋白表达,应用逆转录-聚合酶链反应（RT-PCR）法检测各组肺组织中的TGF-β1和VEGF mRNA表达水平。结果模型组小鼠经过8周过敏原激发后,肺组织病理学发生了较典型的哮喘样改变;地塞米松组和As2O3组小鼠的肺部组织病理学改变较模型组为轻,两组之间无显著差异。模型组小鼠肺组织中TGF-β1、VEGF的蛋白和mRNA表达均增强;与模型组相比,地塞米松组和As2O3组肺组织中TGF-β1、VEGF的蛋白和mRNA的表达均较弱,但仍强于正常对照组。结论致敏后给予8周过敏原激发可成功建立小鼠哮喘气道重塑模型;地塞米松和As2O3治疗均可抑制哮喘的气道重塑过程,其作用机制可能与抑制TGF-β1、VEGF的表达有关。     

糖尿病肾病患者炎症相关因子水平及临床意义

目的探讨炎症相关因子与糖尿病肾病的关系。方法选取2008年1月～2010年1月来本院就诊的糖尿病肾病患者共150例作为研究对象,选择同期来本院进行健康体检的30名健康人群作为对照组,检测各组人群sIL-2R、CRP、TGF-β1和IL-6水平,并进行组间比较。结果健康对照组四种指标水平均低于糖尿病肾病患者,5期糖尿病肾病患者四种指标水平最高,随着患者病情加重,sIL-2R、CRP、TGF-β1和IL-6水平均呈现逐渐增高的趋势(P<0.01)。结论 sIL-2R、CRP、TGF-β1和IL-6与糖尿病肾病的发生发展密切相关,是进行病情判断的重要参考指标。     

Effects of rhein on human articular chondrocytes in alginate beads

This study was designed to investigate the effects of rhein, the active metabolite of diacerhein, on the metabolic functions of human chondrocytes cultured in alginate beads.Enzymatically isolated osteoarthritic (OA) chondrocytes were cultured in alginate beads in a well-defined culture medium for 12 days. Rhein was tested in a range of concentrations comprised between 10(-7) and 4 x 10(-5)M, in the presence or absence of 10(-10)M IL-1beta. Interleukin (IL)-6 and -8, macrophage inflammatory protein (MIP-1beta), stromelysin-1 (MMP-3), aggrecan (AGG), tissue inhibitor of metalloproteinases-1 (TIMP-1), prostaglandin E(2) (PGE(2)) and nitric oxide (NO) productions were assayed. Cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) mRNA steady-state levels were also quantified. In the basal condition, 10(-5)M rhein increased by 46.5% the production of AGG, decreased by 17-30% the production of IL-6, MMP-3, NO and MIP-1beta but enhanced by 50% the production of PGE(2). IL-1beta increased IL-6, IL-8, MIP-1beta, NO, PGE(2) and MMP-3 productions, but inhibited AGG and TIMP-1 synthesis. Rhein partially reversed the effect of IL-1beta on TIMP-1 and NO production, had no effect on AGG, IL-6 and MIP-1beta production, but up-regulated the IL-1beta stimulated PGE(2) production. The COX-2 and iNOS mRNA levels and IL-8 production were not modified by rhein.Overall, these results contribute to explain the clinical efficiency of rhein and give new information on its mechanisms of action.     

胆道闭锁肝纤维化研究进展

胆道闭锁（BA）是严重危及婴幼儿生命健康的消化系统疾病之一,晚期肝脏纤维化是导致患儿死亡的主要原因。在胆道闭锁发病过程中,病毒感染可诱导一系列免疫和炎症反应,导致调节性T细胞（Treg细胞）减少,CD14表达增高,多种炎症通路以及转化生长因子-β（TGF-β）/Smad2/3促纤维化通路被激活。激活的通路产生大量炎性介质损伤肝细胞和胆管细胞,释放各种促炎因子、氧代谢产物和细胞因子,进一步加重肝、胆系统损伤造成肝细胞内环境失衡,失衡的内环境伴随肝实质细胞、肝巨噬细胞、肝内聚集的炎性细胞等发生适应性变性、坏死、增生,导致肝星形细胞（HSCs）激活,HSCs转化为成纤维细胞,促进肝纤维化进程。免疫、炎症损伤、促纤维化通路是导致胆道闭锁肝纤维化肝硬化的三大重要因素。     

固体口服制剂的相转化研究进展

固体口服制剂的相转化研究对选择工艺流程和研发新产品有重要意义。根据相转化机制，固相相变可以分为3种类型：多晶型的转化（polymorphic transition），水化与脱水（hydration／dehydration），玻璃化相与结晶（vierfication/crystallization）的相互转化。固体口服新制剂研究中应重视药物多晶型和无定形现象，预防和防治固相处方设计与工艺流程选择中发送的相转化。