细胞外基质降解酶系统在肾脏疾病中作用的研究

SPECIAL ATTENTION SHOULD BE GIVEN TO THE RESEARCH ON EXTRACELLULAR MATRIX DEGRADATIVE SYSTEMS IN KIDNEY DISEASES

肾脏细胞外基质合成、降解失衡与重塑并最终导致细胞外基质积聚是各种肾病发展至终末期肾衰的共同病理表现 ,而调控细胞外基质代谢的细胞外基质降解酶类的表达与活性异常在其中发挥重要的作用。研究纤溶酶原激活物 /纤溶酶原激活物抑制物(PA/PAI)以及基质金属蛋白酶及其抑制物 (MMP/TIMP)在肾病发生与发展中的作用及其调控已成为热点问题 ,以前偏重于对抑制物(PAI与TIMP)的研究 ,近来研究发现 ,降解酶及其抑制物之间表现出了复杂的动态演变。尽管已经进行了大量的研究 ,但是其确切机制尚未完全阐明。明确PA/PAI与MMP/TIMP系统中各个组成成分在不同的疾病模型或者疾病发展阶段特定的致病作用 ,并解析其遗传与分子调节机制 ,有助于进一步明确慢性进展性肾病的发生发展机制 ,进而通过干预细胞外基质降解酶的活性或表达 ,达到治疗或者预防肾脏疾病的目的。

Alterations in the balance between synthesis and degradation of extracellular matrix (ECM) and its remodeling may result in an accumulation of ECM molecules and lead to glomerulosclerosis. Recent studies have focused on the role of degradative systems, especially the roles of plasminogen activators/plasminogen activator inhibitors (PA/PAI), matrix metalloproteinases, and their inhibitors[GK2*4/5!2*4/5] (MMP/TIMP) in the initiation and pathogenesis of renal diseases. Previously, attention has been paid to the study of inhibitors of ECM degrading enzymes, such as PAI and TIMP. Recent researchs showed that there existed complex dynamic expressions of enzymes and their inhibitors. Although many studies have tried to elucidate the pathogenesis of renal diseases, the exact underlying mechanisms are still not completely understood. For better understanding of the mechanism of chronic progressive renal diseases, the underlying genetic and molecular regulation of each component of PA/PAI and MMP/TIMP systems should be elucidated in different renal physiological and pathophysiological processes. Future studies are needed to manipulate activity or expression of these proteinases in order to treat and/or prevent glomerular diseases.