人纤维介素在急性排斥反应时移植肾组织中的表达及意义

Expression of human fibrinogen-like protein 2 / fibroleukin in renal acute allograft rejection and its potential clinical implication

目的 探讨急性排斥反应时移植肾组织中人纤维介素 [humanfibrinogen likeprotein 2(hfgl2 ) /fibroleukin]的表达及其意义。方法 应用免疫组化法检测 31例急性排斥移植肾穿刺活检标本中hfgl2的表达情况 ,确定阳性表达细胞的细胞类型。做抗纤维蛋白染色、微血栓染色 ,观察急性排斥反应时纤维蛋白沉积及微血栓分布情况 ,同时做抗hfgl2和抗纤维蛋白双染色 ,观察hfgl2的局部促凝作用与纤维素沉积的关系。结果 2 9例急性排斥标本中可见hfgl2表达 ,主要在肾小管上皮细胞、间质浸润细胞和部分黏附、浸润于血管内皮及肾小管上皮细胞间的炎性细胞。间质中部分hfgl2阳性表达细胞的临近区域及部分hfgl2阳性肾小管的管腔内可见纤维蛋白沉积。结论 hfgl2在人同种肾移植急性排斥反应中异常表达 ,局部激活了血管内、外的凝血酶 ,导致纤维蛋白的沉积和微循环障碍 ,从而进一步加重了急性排斥反应时的组织病理损害。hfgl2有可能成为干预急性排斥反应进程的新靶点。

Objective To investigate the expression of human fibrinogen-like protein 2 (hfgl2)/fibroleukin in renal acute allograft rejection and its correlation with the course of the disease. Methods(Thirty-one) samples of aspiration biopsy of renal acute allograft rejection were collected. Histological sections were stained with hemotoxylin and eosin. Polyclonal antibody against hfgl2 was used to detect the expression of hfgl2 protein by immunohistochemistry. Anti-CD68 and anti-CD8 monoclonal antibodies were used to detect the macrophages activation and lymphocyte respectively in serial sections to identify the cell types that express hfgl2. Anti-fibrinogen monoclonal antibody and thrombus staining were used to detect the fibrin deposition and the formation of thrombus. Double staining with anti-hfgl2 antibody and anti-fibrinogen antibody was performed to clarify the correlation between hfgl2 expression and fibrin deposition. Results (Twenty-nine) cases showed hfgl2 expression, mainly displayed in tubule cells, infiltrative cells (macrophages, CD8+ T cells and plasmacytes), and part of the adherent cells or infiltrative cells in tubules and vessels, whereas no hfgl2 protein was detected in glomerulus and endothelium of vessels. Double staining displayed that the fibrin deposition was mainly in the vessels, glomeruli and interstitium, and the lumen of tubule in association with hfgl2 expression. No thrombus was found in all the sections. Conclusion The abnormal expression of hfgl2 in renal acute allograft rejection in human beings activates the thrombosin inside and outside the vessels that causes fibrin deposition and microcirculatory disturbances, thus further exacerbating the pathological injuries of tissues. hfgl2 protein may serve as a new target for therapeutic intervention for acute allograft rejection.