microRNA对基质金属蛋白酶2和基质金属蛋白酶9的调控及其在主动脉瘤发生发展中的作用

主动脉瘤(AA)是一种发病率和死亡率都很高的心血管疾病,且发病机制极其复杂。研究证实microRNA(miRNA)可以调节AA的多种病理生理过程,包括炎症、细胞外基质(ECM)重构、血管平滑肌细胞增殖和死亡等。基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)是MMP蛋白酶家族中的重要成员,同样在AA的上述病理生理过程中起着重要作用。近年来发现多种miRNA可通过直接或间接的方式调节AA中MMP-2和MMP-9的表达和活性,从而影响AA的发生发展。文章主要总结了miRNA对MMP-2、MMP-9的调控机制及其在AA病变中的作用,旨在为AA的诊断和治疗提供新思路。     

性激素和细胞因子与骨关节炎及骨质疏松的关系

骨性关节炎（OA）和骨质疏松（OP）无论从发病部位、病理和生化上均有很大不同，但与性激素均有关。内源性性激素可能是OA高危因素之一，不少研究者认为OA的发生对OP是保护因素。白介素（IL）-1β能促进软骨和滑膜组织基质金属蛋白酶（MMP）s的表达，具骨吸收作用。IL-、IL-6和肿瘤坏死因子（TNF）-α是引起OA炎性病变及软骨降解的重要因素。白血病抑制因子（LIF）能影响关节软骨代谢，参与滑膜炎性病变及骨重建过程，是OA发病的重要调节因子。     

性激素和细胞因子与骨关节炎及骨质疏松的关系

骨性关节炎(OA)和骨质疏松(OP)无论从发病部位、病理和生化上均有很大不同,但与性激素均有关。内源性性激素可能是OA高危因素之一,不少研究者认为OA的发生对OP是保护因素。白介素(IL)-1β能促进软骨和滑膜组织基质金属蛋白酶(MMP)s的表达,具骨吸收作用。IL-1、IL-6和肿瘤坏死因子(TNF)-α是引起OA炎性病变及软骨降解的重要因素。白血病抑制因子(LIF)能影响关节软骨代谢,参与滑膜炎性病变及骨重建过程,是OA发病的重要调节因子。     

干细胞移植治疗骨质疏松

目前治疗原发性骨质疏松症的药物主要作用于骨形成和骨吸收耦联失调,而对骨髓间充质干细胞(MSCs)与骨质疏松关联的治疗方法尚未研制成功。骨髓间充质干细胞的衰老是原发性骨质疏松症的发病机制之一。间充质干细胞衰老,导致干细胞增殖能力下降,成骨分化能力减弱,成脂分化增强,骨组织成分减少,骨矿物质基质减少,脂肪组织增加,最终导致骨量减少,骨纤维结构异常,进而出现骨质疏松。移植自体、同种异体的MSCs或者基因修饰MSCs可以有效增加局部骨量,提高骨密度,增强骨力学强度,改善局部骨质疏松情况,可纠正骨代谢失衡,减少骨量丢失,增加成骨,有望为治疗骨质疏松提供一种新的策略和方法。     

慢性阻塞性肺疾病患者肺组织基质金属蛋白酶2、9的表达与气流阻塞的关系

在慢性阻塞性肺疾病（COPD）发病机制的蛋白酶和抗蛋白酶失衡学说中基质金属蛋白酶（MMP）起主要作用,但MMP-2、MMP-9在肺组织表达的研究较少.为探讨COPD患者发病的影响因素,我们应用免疫组化和逆转录-聚合酶链反应（RT-PCR）方法检测COPD患者MMP-2、MMP-9在肺组织的表达及与气流阻塞的关系.     

基质金属蛋白酶与缺血性脑损伤

动物模型研究显示,脑缺血再灌注时,基质金属蛋白酶(MMP)表达异常,提示其与脑缺血再灌注损伤有关,尤其是MMP-2、MMP-3和MMP-9,在急性缺血性脑血管病的发病机制中起着重要作用.了解MMP在脑缺血再灌注损伤中的表达、作用、影响其表达的因素及有关抗体的研究和应用,可为脑梗死的早期诊断、预防和治疗提供一种新的选择.     

雌激素影响绝经后骨质疏松分子机制研究进展

<正>骨质疏松是以骨量减少、骨的微观结构退化为特征的,致使骨的脆性增加以及易于发生骨折的一种全身性骨骼疾病,可分为三大类即原发性骨质疏松、继发性骨质疏松、特发性骨质疏松。绝经后骨质疏松(PMOP)为Ⅰ型原发性骨质疏松,由绝经后机体雌激素水平下降而引发,年龄通常界定在50~70岁。雌激素的缺乏被认为是PMOP的主要原因,其中具体的分子机制仍未达成共识,本文结合近些年研究雌激素对PMOP发病机     

基质金属蛋白酶与缺血性脑血管病

基质金属蛋白酶(MMP),尤其是MMP-2和MMP-9,在急性缺血性脑血管病的发病机制中起着重要作用。研究表明,它们不但能够降解微血管基底膜和细胞外基质,参与神经系统炎症反应和急慢性神经变性疾病;而且在脑缺血的早期诊断、促进神经元分化和凋亡以及在rtPA溶栓治疗后的出血性并发症中都发挥重要作用。MMP抑制剂的应用已为缺血性脑血管病的治疗提供了一种新的选择。     

细胞外基质分解酶

近年来,随着肝纤维化机制的逐步阐明,基质金属蛋白酶(MMP)——细胞外基质分解酶的重要性越来越受到关注,以活性中心存在Zn~(2 )为特征的MMP基因家族的新分子不断被发现。本文就肝脏中已知的MMP种类及其作用的最新研究进展作一介绍。 一、MMP (一)MMP的类型和结构 MMP是以细胞外基质蛋白为主要底物的一组金属依赖性蛋白酶的总称。近年,数种具有跨膜结构的MMP(membrane-type MMP, MT-MMP)被发现,因而现在主张根据基因结构特征分类。 MMP的基因基本结构由信号肽、前肽、酶活性部位、铰链、血红蛋白结合蛋白类似物5个区域组成,根据与细胞内酶活性有关的弗林蛋白酶识别部位(RXKR)的有无,大致可分成2类,即RXKR型和非RXKR型。前者包括有跨膜结构的4种MT-MMP和无跨膜结构的MMP-11。后者现已分出三型12种,MMP-7(基质溶解素)属短小型,MMP-2、MMP-9属纤维连接蛋白型,最早发现的MMP-1为MMP基本型。 (二)MMP-1、MMP-13 MMP-1是间质型胶原酶,MMP-13又称胶原酶3,可特异性地分解Ⅰ、Ⅱ、Ⅲ型胶原。潜在型MMP-1经纤维蛋白溶酶等丝氨酸蛋白水解酶的限定分解和自身的媒触反应转变为中间活性型,再在MMP-3的作用下而变为活性型MMP-1。MMP-1、MMP-3基因表达的控     

基质金属蛋白酶与缺血性脑血管病

基质金属蛋白酶（MMP），尤其是MMP-2和MMP-9，在急性缺血性脑血管病的发病机制中起着重要作用。研究表明，它们不但能够降解微血管基底膜和细胞外基质，参与神经系统炎症反应和急慢性神经变性疾病；而且在脑缺血的早期诊断、促进神经元分化和凋亡以及在rtPA溶栓治疗后的出血性并发症中都发挥重要作用。MMP抑制剂的应用已为缺血性脑血管病的治疗提供了一种新的选择。     

Secondary osteoporosis and glucocorticoid-induced osteoporosis

In order to assess properly the diagnosis of osteoporosis, a short clinical investigation is required to address potential causes for bone loss. Osteoporosis used to be suspected in a patient with vertebral demineralization, but nowadays it is often diagnosed in a patient with a low bone mass on a screening dual-energy X-ray absorptiometry (DEXA). In this setting, it is important for the clinician to look for secondary osteoporosis, especially in men in whom secondary osteoporosis is more frequent than in women, before discussing any specific therapy. The major causes are longterm glucocorticoid therapy, endocrine (hypogonadism, primary hyperparathyroidism, hyperthyroidism), or digestive diseases.     

Epidemiology of osteoporosis

Osteoporotic fractures represent a significant public health burden, which is set to increase in future generations. Lifetime risk is high and lies within the range of 40% to 50% in women and 13% to 22% in men. Life expectancy is increasing worldwide, and it is estimated that the number of individuals aged 65 years and older will increase from the current figure of 323 million to 1555 million by the year 2050. These demographic changes alone can be expected to cause the number of hip fractures occurring worldwide to increase from 1.66 million in 1990 to 6.26 million in 2050. Based on current trends, hip fracture rates might increase in the United Kingdom from 46,000 in 1985 to 117,000 in 2016. The societal cost of these fractures is high; cost-effectiveness analyses showed cost-effectiveness in treating high-risk patients with antiresorptive drugs, particularly if administered as soon as possible after a first fragility fracture.     

骨质疏松症治疗新进展

骨转换失衡是骨质疏松症发病的重要病理机制,骨质疏松症的治疗靶点主要集中在抑制破骨细胞活性及增强成骨细胞活性。新型骨吸收抑制剂包括核因子-κB受体活化因子配体（RANKL）的单克隆抗体、组织蛋白酶K抑制剂、新型选择性雌激素受体调节剂、口服降钙素等;新型骨形成促进剂有骨硬化素单克隆抗体、Dickkopf-1单克隆抗体、甲状旁腺激素（PTH）制剂及钙敏感受体拈抗剂等。此外,含有维生素D的复方制剂也是很有应用前景的骨质疏松治疗新药。     

骨质疏松症治疗新进展

骨转换失衡是骨质疏松症发病的重要病理机制,骨质疏松症的治疗靶点主要集中在抑制破骨细胞活性及增强成骨细胞活性.新型骨吸收抑制剂包括核因子-kB受体活化因子配体(RANKL)的单克隆抗体、组织蛋白酶K抑制剂、新型选择性雌激素受体调节剂、口服降钙素等;新型骨形成促进剂有骨硬化素单克隆抗体、Dickkopf-1单克隆抗体、甲状旁腺激素(PTH)制剂及钙敏感受体拮抗剂等.此外,含有维生素D的复方制剂也是很有应用前景的骨质疏松治疗新药.     

Epidemiology of osteoporosis

The risk of osteoporotic fracture is lower in Asia and Africa than Caucasian women in the USA and Europe, but worldwide projections showed that it will probably increase markedly in the future. By 2050,the number of hip fracture increased three to four times higher than that in the present, and over half of all hip fracture will occur in Asia. Up to 50% of the variation in peak bone mass may be determined genetically. Sex hormone deficiency plays a major role in development of osteoporosis. In addition, nutrition, physical activity, cigarette smoking, and alcohol consumption also affects bone mass. Modification of these risk factors is important to prevent osteoporosis and consequent fracture in future generations.     

Epidemiology of osteoporosis

Osteoporosis is a major public health problem through its association with fracture. The problem may be alleviated substantially by appropriate early intervention before fracture occurs. This chapter discusses the epidemiology of osteoporosis and addresses the following questions: How should osteoporosis be defined? What is the incidence and prevalence of osteoporosis and fracture? Is there geographical variation in the occurrence of osteoporosis? What are the risk factors for osteoporosis and do they explain the occurrence of osteoporosis and osteoporotic fracture?     

Genetics of osteoporosis

There is clear evidence of genetic modulation of bone phenotype parameters including bone density, quantitative ultrasound, bone size, and bone turnover. At any particular age and phase of life, genetic factors explain about 70% of the variance in bone phenotype after adjustment for major medical and disease factors. Hormonal factors, diet, and lifestyle interact with those genetic factors over time. Common allelic variation in the VDR was the first of several genes and now chromosomal loci to be implicated in the genetic determination of bone phenotype. The VDR polymorphisms have an effect weaker than originally reported, and part of the allelic effects may be mediated by effects on body size and development and even other hormonal regulators such as PTH or insulin. Irrespective of the strength or mechanism of these associations, these initial findings on the VDR stimulated the field of the genetics of osteoporosis with targeted genetic studies and now genome scan approaches. Intronic polymorphisms of the collagen I alpha 1 gene have been shown to be related to bone density and to fracture risk in several studies, although not all findings concur. Common allelic variations have now been associated with bone density for the estrogen receptor, TGF beta receptor, and TGF beta 1, for the insulin-like growth factor-I pathway, for interleukin-4 and -6 and the interleukin-1 receptor antagonist, for calcitonin and the PTH receptors and for apolipoprotein E. Of considerable interest, chromosomal loci, notably 11q 12-13, have now been linked to bone phenotypes in human and mouse studies. The mouse strain studies seem likely to be powerful tools providing insight to important human loci based on the mouse-human chromosomal synteny. Variability of genetic findings across studies seems to be the rule rather than the exception. This variability may relate to interaction of particular loci with specific environmental or even other genetic loci. The importance of genetic heterogeneity, including ethnicity, as well as environmental and hormonal confounders, such as calcium and vitamin D intake, hormonal status and skeletal and body size, will need to be taken into account in future gene search approaches. Genome scans in relation to bone density and fracture end-points will need to account for such important potential confounders in each target population. Interactions between genetic and environmental factors, including lifestyle, have been investigated initially for the VDR polymorphisms in relation to the response of bone density and turnover to calcium intake and treatment with simple vitamin D and active vitamin D compounds. Gene-gene and gene-environment interactions in human and animal models will be critical targets for future research. Further genes with positive and negative effects on bone phenotype are certain to be identified in the near future. Each of these will need to be evaluated in relation to potential environmental modulators in pharmacogenetic models. Understanding the molecular physiology of such gene effects is likely to lead to more specific treatments and to allow the selection of more appropriate and effective treatment options.