大鼠同系与同种肾移植的慢性排斥反应机制的研究

目的　研究大鼠肾移植后非免疫因素在慢性排斥反应发病机制中的作用。方法　对双肾切除的大鼠进行原位同系和同种肾移植 ,并设自体移植对照组。移植术后连续 5 2周对各组的尿蛋白含量、组织形态学和免疫组织化学进行观察。结果　同系移植组 2 4周时尿蛋白逐渐增多 ,小血管周围和肾小球周围出现持续性的单核细胞浸润 ;32周时 ,小管萎缩加重 ,因中膜平滑肌增生而出现小叶间动脉和皮质动脉内膜肥厚病灶 ;5 2周时 ,>30 %的肾小球发生节段性或完全的硬化 ,且几乎所有的动脉出现管腔狭窄 ,小管萎缩与间质纤维化亦非常明显。同种移植组在 12周时即有 >30 %的肾小球硬化 ;32周时 >40 %的肾小球出现完全或节段性的硬化 ,并间质纤维化。同系和同种移植组与自体移植组比较 ,差异均有极显著性 (P <0 .0 1)。结论　非免疫因素引起的同系移植肾功能和形态的变化与同种移植肾慢性排斥反应的早期表现相似 ,对前者而言 ,移植肾的初期损害和有功能的肾组织量是慢性排斥反应发病机制中的重要因素。

Study of chronic kidney isograft and allograft rejection

Objective To study the role of antigen-independent factor in the pathogenesis of chronic rejection of organ transplants.Methods Kidney isografts and allografts were transplanted orthotopically into bilaterally nephroectomized rat recipients and studied functionally, morphologically and immunohistologically, at serial intervals upto 52 weeks after transplantation. Allograft recipients developed progressive protein uria after 12 weeks, with gradual renal failure ultimately leading to death. Results Simultaneously, morphologic changs, including progressive arteriosclerosis and glomerulosclerosis, tubular atrophy and interstitial fibrosis, deveploped. Immunohistologically, macrophages infiltrated glomeruli during this period and cytokines were unregulated.Conclusion Antigen-independent functional and morphologic changes occur in long-term kidney isografts that resemble those appearing considerably earlier in allografts that reject chronically. Initial injury and extent of functioning renal mass is an important factor for such late changes.