To elucidate the molecular mechanism on anti-arrhythmic function of Dingxin Recipe (DXR). Methods: Cardiac myocytes isolated by trypsin method were cultured and labeled with various fluorescence stains. DXR contained serum induced changes of cellular calcium concentration 〔Ca2＋〕i, cell membrane potential (MP) and mitochondria membrane potential (MMP) were determined with laser confocal microscopy. Results: Hypoxia caused increase of 〔Ca2＋〕i and MMP, and decrease of MP, while DXR contained serum lowered the 〔Ca2＋〕i in normal or hypoxic myocytes, improved hypoxia induced MP reduction and maintain MMP at baseline level under hypoxia circumstances. Conclusion: Through inhibiting the hypoxia caused 〔Ca2＋〕i and MMP elevation and MP lowering, DXR displays its action in protecting myocardial cells to prevent and treat arrhythmia.

冠心病分子机制研究进展

根据多年的研究,目前已知冠心病的发生是一个多种因素综合作用下的多个环节的复杂慢性炎症过程.其各种危险因素间及其各个环节间还具有复杂的交互作用,多种分子及细胞相互作用形成复杂的网络,本年度冠心病分子机制的研究在下列几个方面值得关注.

Mecobalamin, a form of vitamin B12 containing a central metal element (cobalt), is one of the most important mediators of nervous system function. In the clinic, it is often used to accelerate recovery of peripheral nerves, but its molecular mechanism remains unclear. In the present study, we performed sciatic nerve crush injury in mice, followed by daily intraperitoneal administra-tion of mecobalamin (65 μg/kg or 130 μg/kg) or saline (negative control). Walking track analysis, histomorphological examination, and quantitative real-time PCR showed that mecobalamin signiifcantly improved functional recovery of the sciatic nerve, thickened the myelin sheath in myelinated nerve ifbers, and increased the cross-sectional area of target muscle cells. Further-more, mecobalamin upregulated mRNA expression of growth associated protein 43 in nerve tissue ipsilateral to the injury, and of neurotrophic factors (nerve growth factor, brain-derived nerve growth factor and ciliary neurotrophic factor) in the L4–6 dorsal root ganglia. Our ifndings indicate that the molecular mechanism underlying the therapeutic effect of mecobalamin after sciatic nerve injury involves the upregulation of multiple neurotrophic factor genes.

Transmissible spongiform encephalopathy or prion disease is triggered by the conversion from cellular prion protein to pathogenic prion protein. Growing evidence has concentrated on prion protein configuration changes and their correlation with prion disease transmissibility and pathoge-nicity. In vivo and in vitro studies have shown that several cytosolic forms of prion protein with spe-cific topological structure can destroy intracellular stability and contribute to prion protein pathoge-nicity. In this study, the latest molecular chaperone system associated with endoplasmic reticu-lum-associated protein degradation, the endoplasmic reticulum resident protein quality-control system and the ubiquitination proteasome system, is outlined. The molecular chaperone system directly correlates with the prion protein degradation pathway. Understanding the molecular me-chanisms wil help provide a fascinating avenue for further investigations on prion disease treatment and prion protein-induced neurodegenerative diseases.

雪旺氏细胞在周围神经损伤修复中的作用及其分子机制

雪旺氏细胞是周围神经系统中特有的胶质细胞,在周围神经损伤后的变性和再生中有着非常重要的作用.周围神经的再生主要依赖于雪旺氏细胞提供了适宜的微环境,如分泌多种神经营养因子和其它相关因子,位于轴突和雪旺氏细胞之间的紧密连接加强信息传递,雪旺氏细胞形成Büngner带为轴突生长的通道,并形成髓鞘等.本文阐述了雪旺氏细胞在周围神经再生中的重要功能以及相关机制,展望围绕雪旺氏细胞的未来研究方向,临床应用的潜在价值.

熊去氧胆酸对肝细胞凋亡作用的分子机制

熊去氧胆酸足人胆汁的生理成分,占正常人总胆汁酸的1%～3%[1].它是一亲水性强,去垢性差,几乎无毒件的胆汁酸.具有利胆、细胞保护和拮抗疏水性胆汁酸的细胞毒性等作用.已广泛在临床上用于治疗原发性硬化性胆管炎、原发性胆汁性肝硬变和妊娠肝内胆汁淤积症等.近年来发现UDCA具有抗肝细胞凋亡作用,并对其作用机制有了一定了解.

K离子通道在剪切力诱导血管内皮细胞信号转导中的作用

血液在血管中流动时对血管壁产生持续的作力,分为剪切力、周向应力和压应力[1],剪切力在心血管系统的许多病理及病理生理过程中起着重要而跃的作用[2],它可以影响血管内皮细胞的形态及功能,导致应激的和缓慢的组织应答.剪切力信号通过血管内皮细胞的转导主要通过细胞骨架与生化因的相互作用,并引起内皮细胞结构、代谢及基因表达的变化[3,4].但长期以来,剪切力诱导内皮细胞形态学和功能的改变未能受到足够的重视,本综述描述了剪切力信号转导的可能途径,重点是离子通道(特别是K+通道)对剪切力的应答以及由此引起的细胞反应.

AIM:There is little evidence proving the molecular mechanism of WenxinKeli ( WXKL) .This study tried to explore the gene ex-pression profile and pathology alteration of WXKL-treated rabbits with myocardial infarction .METHOD: Twenty male adult rabbits were randomly divided into 4 groups:sham, model, WXKL and captopril groups .Model, WXKL and captopril groups underwent the ligation of the left anterior descending coronary artery , while sham group went through an identical procedure without ligation .WXKL (817 mg? kg-1? d-1), captopril (8 mg? kg -1? d-1) and distilled water (model and sham) were administered orally to the rabbits. 4 weeks later, hearts were taken out for expression chip and pathological staining (HE, Masson and TUNEL) after echocardiography. RESULT:WXKL could down-regulate genes associated with inflammation (CX3CR1, MRC1, and FPR1), apoptosis (cathepsin C and TTC5) and neuro-hormonal system (ACE and EDN1), and up-regulate angiogenesis promoting gene like RSPO 3, which explained why WXKL group represented with better cardiac function , less histopathological injury and slighter apoptosis .CONCLUSION:WXKL plays an important role in suppressing inflammation , inhibiting renin-angiotensin system and alleviating apoptosis , and might be a promising Chinese medicine in treating patients with myocardial infarction .

先天性肾缺如及发育不全的分子机制研究进展

先天性肾缺如(renal agenesis,RA)及发育不全(renal dysplasia,RD)是先天性肾脏及尿路畸形(congenital anomalies of the kidney and urinary tract,CAKUT)中常见、严重的形式之一,部分患者可隐匿进展至终末期肾衰竭,故越来越多的研究者致力于其机制的研究.除物理及化学因素外,遗传因素在发病机制中的地位备受重视.近年来,通过对基因敲除小鼠模型及包括RA或RD畸形综合征的研究,研究者发现众多参与后肾发育调控网络的基因缺陷均可导致RA或RD.本文从人类肾脏胚胎发育的角度,结合文献,综述RA及RD的有关分子机制研究的进展.

肺重复癌发生机制和诊断预测的研究进展

Due to the advanced diagnostic technique and better understanding for multiple primary lung cancers (MPLC), the increasing incidence of MPLC has been reported. Very often, MPLC are misdiagnosed as metastasis because of lacking efficient molecular biomarkers for prediction and diagnosis. Studies on the molecular mechanism for tumorgenesis and progression of MPLC may therefore facilitate the discovery of biomarkers for disease diagnosis and prognosis, so that an individual and rational treatment can be achieved. We tried to further our understanding and improve the diagnostic skill for MPLC by reviewing the current status and the latest advancement of molecular markers related to MPLC.

核苷类似物耐药相关分子通路的研究进展

乙型肝炎是一种严重危害人类健康的世界性传染病.据估计,目前全球约有3.8亿慢性乙型肝炎患者.我国是乙型肝炎病毒(HBV)高流行区,总人口的8%～10%为乙肝病毒表面抗原(HBsAg)携带者,慢性乙型肝炎患者有两千多万人.积极治疗慢性乙型肝炎、促进人民健康、防止病情进一步发展成为肝硬化乃至肝细胞肝癌,是我们面临的一项刻不容缓的任务.

氯喹抗药性的分子药理学作用研究进展

氯喹是治疗和预防疟疾有价值的药物.它的药理学作用靶点是血阶段疟原虫的食物消化泡.其作用过程普遍认为氯喹与疟原虫消化血红蛋白后所释放的血红素结合,形成一种复合物-氯高铁血红素(Hemin),因此阻止了疟原虫消化血红蛋白,形成无毒的疟色素(Hemozoin)[1,2].通过这样的过程,产生一种游离基团,破坏疟原虫食物消化泡内的各种酶,如磷酸脂酶、蛋白酶和胞膜[3,4].然而,抗氯喹恶性疟原虫是如何改变了这一过程却知之甚少.随着分子生物学技术的不断发展,对其药理学作用的认识也不断加深.本文对氯喹抗药性的分子药理学作用研究进展做了概述.

The Molecular Mechanisms of Nm23-H1 Gene Transfection on Reversing Invasion and Metastasis Phenotype in Human High-metastataic Large Cell Lung Cancer Cell Line L9981

Background: Our previous studies have proved that nm23-Hl gene was a tumor metastatic suppressive gene, tumor metastasis phenotype of human lung cancer could be reversed by transfection of nm23-H1 cDNA, but the molecular mechanism of nm23-H1 for inhibiting tumor invasion and metas-tasis is unclear. The aim of this study is to explore the molecular mechanism of nm23-Hl reversing the invasion and metastasis phenotype in human high-metastatic large cell lung cancer line L9981.

1 IntroductionRecent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer. Sequencing of human genome has identified many oncogenes and tumor suppressor genes,giving us a better understanding of the molecular events leading to the formation, progression, metastasis, and the development of drug resistance in human lung cancer. In addition, many signal transduction pathways have been discovered that play important roles in lung cancer. Novel strategy of anti-cancer drug development now involves the identification and development of targeted therapy that interrupts one or more than one pathways or cross-talk among different signal transduction pathways. In addition, efforts are underway that combine the traditional cytotoxic (non-targeted) agents with the biological (targeted) therapy to increase the response rate and survival in patients with lung cancer, especially advanced non-small cell lung cancer (NSCLC).

Osteoarthritis (OA) is a common joint degenerative disease affecting the whole joint structure, including articular cartilage, subchondral bone and synovial tissue. Although extensive work has been done in recent years to explore the molecular mechanism underlying this disease, the pathogenesis of OA is still poorly understood and currently, there is no effective disease-modifying treatment for OA. Recently, both in vitro and in vivo studies suggest that confirmed (TGF-b)/SMAD pathway plays a critical role during OA development. This short review will focus on the function and signaling mechanisms of TGF-b/SMAD pathway in articular chondrocytes, mesenchymal progenitor cells of subchondral bone and synovial lining cells during OA development.