从细胞生物学角度深入研究活化凝血因子参与慢性进行性肾损伤的机制

IN DEPTH STUDY OF THE MECHANISMS OF ACTIVATED COAGULATION FACTORS INVOLVED IN THE PATHOGENESIS OF CHRONIC PROGRESSIVE RENAL INJURY BY CELLULAR BIOLOGICAL METHODS

传统观点认为，肾小球内凝血导致慢性进行性肾损伤的主要机制是微血栓形成引起肾小球缺血性损伤。近年来作者采用细胞生物学方法，观察了活化凝血因子凝血酶和纤维蛋白对肾小球内皮细胞（ＧＥＣ）和系膜细胞的直接影响，发现凝血酶可以诱导ＧＥＣ增殖、细胞外基质降解增加以及细胞脱壁；纤维蛋白可以支持ＧＥＣ铺展、增殖，并可以诱导ＧＥＣ单层结构破坏和血管样结构形成，同时可以上调胞间粘附分子－１（ＩＣＡＭ－１）的表达。凝血酶还可以促进系膜细胞增殖、表达ＩＣＡＭ－１、纤溶酶原激活物抑制物－１（ＰＡＩ－１）、基质金属蛋白酶－２（ＭＭＰ－２）及基质金属蛋白酶－９（ＭＭＰ－９）。据此认为，肾小球内凝血可以通过活化凝血因子对ＧＥＣ和系膜细胞的直接作用，转化为炎症反应，并影响细胞外基质的重塑。

Traditionally, it was believed that renal injury caused by intraglomerular coagulation could be attributed to glomerular ischemia due to microthrombosis. Using cellular biological methods, we observed the effects of activated coagulation factors including thrombin and fibrin on glomerular endothelial cells(GEC) and mesangial cells. Results showed that thrombin induced GEC proliferation, extracellular matrix degradation, as well as GEC detachment; fibrin not only supported GEC attachment, spreading, and proliferation, induced GEC monolayer disorganization and capillary structure formation, but also promoted ICAM1 expression. Thrombin promoted proliferation of mesangial cells, and enhanced the expression of ICAM1, MMP2, and MMP9 in mesangial cells. It is concluded that intraglomerular coagulation might shift to inflammatory reaction and influence the remodelling of extracellular matrix by the direct effect of activated coagulation factors on GEC and mesangial cells.