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目的:研究并比较环孢素A(CsA)转换为雷帕霉素(Rapa)与CsA持续使用对大鼠移植肾的长期作用。方法:建立大鼠慢性移植肾肾病模型并分组:CsA转换为Rapa组(第1组,n=10)、CsA持续使用组(第2组,n=10)、CsA撤离组(第3组,n=8)和控制对照组(第4组,n=8)予以安慰剂至第24周。另6只Lewis→Lewis同系移植作为同系移植组(T组)。每4周查24 h尿蛋白定量,24周时处死动物,获取移植肾标本行组织学和免疫组化研究并检测转换生长因子β1和血小板源性生长因子A链的表达。结果:对比控制对照组(第4组),CsA和Rapa的使用(第1,2,3组)均显著地降低了尿蛋白的排泄量;CsA转换为Rapa(第1组)较CsA的持续使用(第2组)进一步降低了尿蛋白的排泄,在第24周差异有统计学意义(P=0.006)。CsA和Rapa的使用(第1,2,3组)大体保护移植肾组织学破坏;而对比CsA持续使用或撤离(第2、3组),CsA转换为Rapa(第1组)则进一步地降低了移植肾组织学Banff评分、显著地减少了肾组织中浸润的炎性细胞数、TGF-β1和α-SMA的染色强度以及转换生长因子β1和血小板源性生长因子A链的mRNA的表达量。结论:CsA转换为Rapa减少了移植肾远期尿蛋白的排泄,减缓远期移植肾组织学的损害并下调了纤维相关基因的表达,可能改善临床移植肾的远期成功率。
OBJECTIVE: To study and compare the long-term effects of cyclosporin A (CsA) conversion to Rapa and CsA on rat renal allografts. Methods: The model of chronic renal allograft nephropathy was established and divided into three groups: CsA group (n = 10), CsA group (n = 10), CsA group n = 8) and control controls (group 4, n = 8) were given placebo until week 24. Another six Lewis → Lewis homotransplantation as a homograft group (T group). The proteinuria of 24 h was examined every 4 weeks. After 24 weeks, the animals were sacrificed and histological and immunohistochemical studies of transplanted kidney were performed to detect the expression of transforming growth factor β1 and platelet-derived growth factor A chain. RESULTS: The use of CsA and Rapa (groups 1, 2, and 3) significantly reduced urinary protein excretion compared with the control control group (group 4); the conversion of CsA to Rapa (group 1) was longer than that of CsA Uses (Group 2) further reduced urinary protein excretion, with a statistically significant difference at Week 24 (P = 0.006). The use of CsA and Rapa (Groups 1, 2, and 3) generally protected renal allograft from damage; while CsA continued to be used or evacuated (Groups 2 and 3) and CsA to Rapa (Group 1) decreased further The renal allograft Banff score significantly reduced the number of infiltrating inflammatory cells in renal tissue, the staining intensity of TGF-β1 and α-SMA and the mRNA expression of transforming growth factor β1 and platelet-derived growth factor A chain . CONCLUSIONS: The conversion of CsA to Rapa reduces excretion of excretion of urinary protein in long-term renal transplantations, slows the damage of long-term renal allograft histology and down-regulates the expression of fiber-related genes, which may improve the long-term success rate of clinical graft kidney.