凝血酶敏感蛋白-1在慢性移植肾病大鼠肾组织中的表达及意义

摘要

目的:探讨大鼠肾组织凝血酶敏感蛋白-1的表达与慢性移植肾病的关系.方法:依照国际标准CAN实验大鼠模型,以F344大鼠作供者,Lewis大鼠作受者,行原位异体肾移植,建立大鼠CAN模型,作为CAN组.以Lewis大鼠做供、受体,行原位异体肾移植,作为对照组.16周后,观察两组大鼠肾功能、肾组织学改变;免疫组织化学法检测肾组织TSP-1及TGF-β1的表达.结果:与对照组比较,CAN组大鼠24 h尿蛋白定量、血肌酐明显升高(P＜0.01);根据Banff97评分标准,对照组未见明显病理改变,而CAN组肾小球硬化率达24%以上,可见明显的肾小管萎缩、间质纤维化及严重的血管内膜纤维化,两组移植肾Banff评分结果差异显著(P＜0.01);TSP-1在对照组弱表达,TGF-β1仅有少量表达,而CAN组TSP-1、TGF-β1阳性表达面积显著增强,可见于肾小球系膜细胞、肾小管上皮细胞、肾间质细胞.结论:TSP-1在CAN大鼠移植肾组织中高表达,可能作为TGF-β1的上游分子参与TGF-β1介导的慢性移植肾病变的发生发展.%Objective To investigate the expression of TSP-1 in transplanted rat kidney and its relationship with CAN. Methods Fisher344 rat renal grafts were orthotopically transplanted into Lewis rats (CAN group), Lewis-to-Lewis kidney transplantations were also performed as the control group. 16 weeks posttransplantation, the animals were sacrificed to harvest sera and renal allografts. The urinary albumin excretion and serum creatinine were measured and pathological changes assessed according to Banff 97 criteria. The expression of TSP-1 and TGF-pi in renal tissues were observed by immunohistochemistry. Result Compared with the control group, CAN rats 24 h urinary protein, serum creatinine was significantly higher, the difference was statistically significant (/*<0.01). According to Banff 97 standard, no obvious pathological changes in the control group, and more than 24% glomerular sclerosis occurred in The CAN group. Renal function deteriorated progressively in the CAN group,and there was typical obvious tubular atrophy, interstitial fibrosis and severe intimal fibrosis observed in the kidneys. Banff score results of the two groups of renal transplantation were significant differences statistically significant (P < 0.01). In the control group, there was low expression of TSP-1 and TGF-B1, However there was high expression of TSP-1 and TGF-B1 and glomerular mesangial cells, renal tubular epithelial cells, renal interstitial cells were found in CAN group. Conclusion There was high expression of TSP-1 in renal tissues of rats with CAN, it suggests that TSP-1 plays an important role in the progression of CAN.