金属硫蛋白及其在肝豆状核变性研究中的应用

综述了金属硫蛋白的结构和生物学特征以及生命活动中的作用。肝豆状核变性的发病机制、动物模型和治疗的研究，均与金属硫蛋白有着密切的关系。     

金属硫蛋白与肝豆状核变性

肝豆状核变性发病的异常蛋白学说目前正受到重视。本文概述了近年来金属硫蛋白的研究进展,并介绍了肝豆状核变性中金属硫蛋白的异常变化以及金属硫蛋白在肝豆状核变性发病机理中的作用。     

特发性间质性肺炎基础和临床研究的几点进展

以特发性肺纤维化(IPF)为代表的特发性间质性肺炎(IIPs)一直是呼吸系统疾病诊治的难点和研究热点。近年来,国内外学者对其分类、发病机制、临床和病理诊断以及治疗等方面进行了广泛而深入的研究。现就基础和临床研究的几点进展概述如下。一、IPF发病机制研究方面的进展肺纤维化发病机制仍是众多学者研究的热点。近年来国内外学者在继续关注肺纤维化形成过程中信号传导、基质金属蛋白酶、细胞因子网络等因素的作用的同时,经研究发现,Ⅱ型肺泡上皮细胞损伤和凋亡是肺纤维化的重要早期特征。日本学者Maeyama等[1] 进行的博莱霉素致肺纤维化…     

金属硫蛋白与糖尿病

氧化应激在糖尿病及其并发症的发病中起重要作用。金属硫蛋白(MT)是一类广泛存在于生物细胞内的低分子量、富含半胱氨酸的金属结合蛋白,对于抵抗有毒金属的毒性及维持一些必需金属在体内的代谢平衡有重要意义。近年研究发现,MT是潜在的抗氧化剂,具有清除体内自由基,抗氧化应激作用,可能对糖尿病具有保护作用。     

间质性肺疾病的发病机制

近年来,肺纤维化发病机制研究取得了许多非常重要的进展,尤其在蛋白水平上.本文基于目前国内外对肺纤维化的研究进展,对其发病机制作扼要综述.     

细胞因子对肺纤维化的影响及其作用机制研究进展

肺纤维化是不同病因所致各种肺间质疾病的共同结局,近年其发病率及病死率呈增高趋势,目前国内外多数学者认为,炎症细胞及其释放的多种细胞因子在肺纤维化的发病机制中起着中心环节的作用.本文对目前肺纤维化相关细胞因子及其作用机制研究进展作一简要概述.     

离体大鼠心肌缺血后再灌注损伤及其保护

利用大鼠离体心脏缺血后再灌注模型,用顺磁共振谱仪检测自由基信号及线粒体比表面的测算,研究与比较金属硫蛋白及辅酶Q_(10)对缺血后再灌注损伤的保护作用。结果表明,这两种物质都有明显的细胞保护作用,而金属硫蛋白的清除氧自由基的能力更为明显。金属硫蛋白是个有希望的细胞保护剂。     

乙型肝炎病毒抗原与金属硫蛋白相互作用的研究

目的 为探讨乙型肝炎病毒(HBV)抗原在乙型肝炎发病机制中的作用，寻找防治HBV感染的有效方法，筛选并克隆人肝细胞中与HBV抗原相互作用的蛋白基因。方法 应用酵母双杂交系统3构建HBV抗原诱饵质粒，转化酵母细胞AH109并在其中表达，与含肝文库质粒的酵母Y187进行配合、双杂交，在营养缺陷培养基(SD／Trp-Leu-His-Ade)上及X-α-gal蓝白斑双重筛选与肝细胞蛋白结合的蛋白编码基因，进一步用网织红细胞裂解物体外翻译、蛋白间免疫共沉淀实验证实其相互作用的可靠性。结果 成功地筛选出HBV前-S2抗原、e抗原(HBeAg)、核心抗原(HBcAg)、X抗原(HBxAg)的肝细胞结合蛋白，发现均有含金属硫蛋白基因的菌落。体外免疫共沉淀技术再次证实金属硫蛋白与HBeAg、HBcAg及HBxAg间有确切的结合作用。结论 金属硫蛋白能与HBV的多种抗原成分结合，在致肝细胞损伤过程中可能起着重要作用。     

基质金属蛋白酶与肺纤维化

基质金属蛋白酶是一类含锌的蛋白水解酶,主要功能是降解细胞外基质的多种蛋白成分,本文综述了基质金属蛋白酶的概况,在肺纤维化中的作用和药物干预对其的影响。     

基质金属蛋白酶-9与肺纤维化

基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)是一种金属离子依赖的蛋白酶,通过多种途径参与特发性肺纤维化(idiopathic pulmonary fibrosis,IPF)的发病机制,本文就MMP-9的基本特性及其与肺纤维化的关系进行综述。     

Oxidative stress is bane in chronic liver diseases: Clinical and experimental perspective

Oxidative stress plays an important role in the pathogenesis of various chronic liver diseases (CLD) and increasing evidence have confirmed the contributory role of oxidative stress in the pathogenesis of drugs and chemical-induced CLD. Chronic liver injury is manifested as necrosis, cholestasis, fibrosis, and cirrhosis. Chronic administration of anti-tubercular, anti-retroviral, immunosuppressive drugs is reported to induce free radical generation during their biotransformation in the liver. Further, these reactive intermediates are said to induce profibrogenic cytokines, several inflammatory markers, collagen synthesis during the progression of hepatic fibrosis. Oxidative stress and free radicals are reported to induce activation and proliferation of hepatic stellate cells in the injured liver leading to the progression of CLD. Hence, to counteract or to scavenge these reactive intermediates, several plant-derived antioxidant principles have been effectively employed against oxidative stress and came out with promising results in human and experimental models of CLD. This review summarizes the relationships between oxidative stress and different liver pathogenesis induced by drugs and xenobiotics, focusing upon different chronic liver injury induced by alcohol, antitubercular drugs and hyperactivity of antiretroviral drugs in HIV patients, viral hepatitis infection induced oxidative stress.     

抗肺纤维化药物研究进展

肺纤维化是严重危害人类健康的公共卫生问题,诊断后中位生存期仅为2～3年,目前已有的抗肺纤维化药物疗效甚微.随着肺纤维化发病机制的进展,多种潜在的抗肺纤维化药物靶点被发现.本文概述肺纤维化的流行病学情况、病因和发病机制,重点介绍作用于炎症、氧化应激、肺泡上皮细胞、肌成纤维细胞等靶点的抗肺纤维化药物的开发现状及展望.     

Wnt信号转导通路与肝纤维化关系的研究现况

阻断该通路可以 Wnt 信号转导通路是近年来分子生物学、细抑制癌细胞的增殖和诱导凋亡.胞生物学和肿瘤研究中的一大热点,其参与调 控细胞分化、癌变、凋亡及机体免疫、应激 等多种病理生理过程.目前许多关于癌症方面 的研究均已证实,阻断Wnt 信号通路可以诱导 癌症细胞的凋亡.肝纤维化的发生与多种信号 通路的激活相关,有研究...     

Actualités dans la physiopathologie de la sclérodermie systémique : vers de nouvelles opportunités thérapeutiques

Systemic sclerosis is a rare connective tissue disease characterized by skin and several internal organ fibrosis, systemic vasculopathy and immune abnormalities. Even if fibroblasts and endothelial cells dysfunction, as well as lymphocytes and other immune cells implication are now well described, the exact origin and chronology of the disease pathogenesis remain unclear. Oxidative stress, influenced by genetic and environmental factors, seems to play a key role. Indeed, it seems to be implicated in the early phases of fibrosis development, vasculopathy and in immune tolerance abnormalities shared by all patients, although disease expression is heterogeneous. To date, no curative treatment is available. Even if immunosuppressive treatment or drugs acting on vascular system are proposed for some patients, overall, treatment efficiency remains modest. Only autologous hematopoietic stem cells transplantation, reserved for patients with severe or rapidly progressive fibrosis, has recently demonstrated efficiency, with lasting regression of fibrosis. Nevertheless, this treatment can expose to important, life-threatening toxicity. In the last decade, new mechanisms implicated in the pathogenesis of systemic sclerosis have been unraveled, bringing new therapeutic opportunities. In this review, we offer to focus on recent insights in the knowledge of systemic sclerosis pathogenesis and its implication in current and future medical care.     

Oxidative stress in the pathogenesis of diffuse lung diseases: A review

Oxidative stress is an imbalance between oxidants (reactive oxygen and nitrogen species) and antioxidants that may affect lipids, DNA, carbohydrates and proteins. The lung is continuously exposed to endogenous and exogenous oxidants (cigarette smoke, mineral dust, ozone, radiation). Reactive oxygen and nitrogen species are mainly produced by phagocytes as well as by polymorphonuclear, alveolar, bronchial and endothelial cells. A potential role of oxidative stress in the pathogenesis of diffuse lung diseases (particularly idiopathic pulmonary fibrosis) has been demonstrated. Increased oxidant levels and decreased antioxidant defences can contribute to the progression of idiopathic pulmonary fibrosis and other diffuse lung diseases.The growing number of papers on the different aspects of oxidant/antioxidant imbalance in diffuse lung diseases in the last decade reflects increasing interest in this topic and suggests that specific DLDs may be characterized by specific patterns of oxidation and antioxidant responses. The study of oxidative stress can provide insights into etiopathogenesis and favour the discovery of new treatments. In this review of the literature on oxidants and antioxidants in diffuse lung diseases, the focus is on idiopathic pulmonary fibrosis, sarcoidosis, pneumoconiosis and pulmonary fibrosis associated with systemic sclerosis.     

Interplay between oxidative stress and hepatic steatosis in the progression of chronic hepatitis C

BACKGROUND/AIMS: The contribution of oxidative stress to the pathogenesis of chronic hepatitis C (CHC) is still poorly elucidated. This study investigated the relationship between oxidative stress, insulin resistance, steatosis and fibrosis in CHC. METHODS: IgG against malondialdehyde-albumin adducts and HOMA-IR were measured as markers of oxidative stress and insulin resistance, respectively, in 107 consecutive CHC patients. RESULTS: Oxidative stress was present in 61% of the patients, irrespective of age, gender, viral load, BMI, aminotransferase level, histology activity index (HAI) and HCV genotype. Insulin resistance and steatosis were evident in 80% and 70% of the patients, respectively. In the patients infected by HCV genotype non-3, but not in those with genotype 3 infection HOMA-IR (p<0.03), steatosis (p=0.02) and fibrosis (p<0.05) were higher in the subjects with oxidative stress than in those without. Multiple regression analysis revealed that, HOMA-IR (p<0.01), fibrosis (p<0.01) and oxidative stress (p<0.05) were independently associated with steatosis, whereas steatosis was independently associated with oxidative stress (p<0.03) and HOMA-IR (p<0.02). Steatosis (p<0.02) and HAI (p=0.007) were also independent predictors of fibrosis. CONCLUSIONS: In patients infected by HCV genotype non-3, oxidative stress and insulin resistance contribute to steatosis, which in turn exacerbates both insulin resistance and oxidative stress and accelerates the progression of fibrosis.     

RhoA在肝纤维化中的作用机制

肝纤维化发生的关键在于肝星状细胞（HSC）转化为成纤维母细胞及活化后细胞外基质（ECM）的异常表达。回顾了Rho/ROCK信号通路在HSC的激活中的重要作用。总结了RhoA,作为Rho/ROCK信号通路上小G蛋白家庭成员之一,且作为一种重要的调节肌动蛋白细胞骨架和细胞形态异质性的细胞因子,参与肝纤维化的进程。指出RhoA在肝脏纤维化发生发展过程中起着重要的调控作用,归纳了RhoA通过调节肌动蛋白应力纤维的装配,并通过级联放大效应影响细胞基质的合成和收缩,最终影响肝纤维化的进展。就RhoA在肝纤维化过程中的机制以及RhoA作为潜在的治疗靶点作一综述。     

Role of differential signaling pathways and oxidative stress in diabetic cardiomyopathy

Diabetes mellitus increases the risk of heart failure independently of underlying coronary artery disease, and many believe that diabetes leads to cardiomyopathy. The underlying pathogenesis is partially understood. Several factors may contribute to the development of cardiac dysfunction in the absence of coronary artery disease in diabetes mellitus. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Hyperglycemia-induced oxidative stress is a major risk factor for the development of micro-vascular pathogenesis in the diabetic myocardium, which results in myocardial cell death, hypertrophy, fibrosis, abnormalities of calcium homeostasis and endothelial dysfunction. Diabetes-mediated biochemical changes show cross-interaction and complex interplay culminating in the activation of several intracellular signaling molecules. Diabetic cardiomyopathy is characterized by morphologic and structural changes in the myocardium and coronary vasculature mediated by the activation of various signaling pathways. This review focuses on the oxidative stress and signaling pathways in the pathogenesis of the cardiovascular complications of diabetes, which underlie the development and progression of diabetic cardiomyopathy.     

Comparison of cardiac lesions induced in rats by isoproterenol and by repeated stress of restraint and water immersion with special reference to etiology of cardiomyopathy

Cardiac lesions induced in rats by isoproterenol, a potent beta-agonist, and by repeated stress of restraint and water immersion, in which sensitization of beta-adrenergic receptors would be expected to be induced, were investigated morphologically and following facts were revealed. 1) Cardiac lesions induced by isoproterenol, characteristic findings of which were myocardial hypertrophy, myocardial degeneration and myocardial necrosis replaced by interstitial fibrosis, were more analogous to cardiomyopathy than myocardial infarction or cardiac hypertrophy. 2) Cardiac lesions induced by repeated stress of restraint and water immersion, characteristic findings of which were myocardial hypertrophy, myocardial degeneration and myocardial necrosis replaced by interstitial fibrosis, were similar to those induced by isoproterenol. These results suggest that the endogenously induced dominant beta-adrenergic stimulating action during stress may play an important role in the pathogenesis of cardiomyopathy, the specific etiology of which is not yet known.     

氧化应激与自噬在肝细胞癌发生发展中的作用

肝细胞癌(HCC)是肝脏的原发恶性肿瘤,其发生过程十分复杂,氧化应激学说是其发生发展机制研究的众多重要学说之一。自噬是细胞清除胞内错误折叠的蛋白质或受损细胞器,维持内环境稳态的重要方式。越来越多的证据显示自噬在肝纤维化和HCC中发挥重要作用,且与氧化应激有密切关系。结合当前国内外最新研究成果,分别从自噬与HCC的关系、氧化应激与HCC的关系来分析二者在HCC发病机制中的相互作用。指出自噬在HCC发病进程中调控氧化应激的分子机制可能成为今后的研究热点,若能够激活或阻断自噬调控氧化应激的某个关键通路,或可为HCC的早期诊断及治疗提供新的手段。