雌激素预防大鼠同种肾移植慢性排斥反应的实验研究

Efficacy of estrogen in preventing chronic renal allograft rejection in rats

目的 探讨雌激素对移植肾慢性排斥反应的影响。方法 以Fisher大鼠作供者 ,雌性Lewis大鼠作受者进行同种肾移植 ,为排除排卵周期及相应的内源性性激素变化的影响 ,肾移植均在非排卵期进行。移植后治疗组大鼠隔日给予 2 5 μg/kg雌二醇皮下注射。移植后 16周作肾功能、移植肾组织学及免疫组化检测 ,测定肾组织中转化生长因子及 β 机动蛋白mRNA的表达。 结果 与对照组比较 ,移植后治疗组 2 4d尿蛋白持续保持较低的水平 (P <0 .0 1) ,血清肌酐水平降低 (P <0 .0 1) ,肌酐清除率升高 (P <0 .0 1) ,移植肾组织血管内膜增厚、肾小球硬化和间质纤维化程度减轻 (P均 <0 .0 1) ,淋巴细胞和单核 /巨噬细胞浸润减少 (P <0 .0 1) ,细胞间粘附分子 (ICAM 1)、转化生长因子 (TGF β1)的mRNA表达减少 (P均 <0 .0 1)。结论 雌激素对移植肾功能有保护作用 ,其机理与影响上述细胞因子在移植肾的表达有关 。

Objective Standard rat model of chronic renal allograft rejection was used to evaluated the effect of estrogen on chronic renal rejection. Methods Kidney transplantation was performed with male/female Fisher rats as donors and female Lewis rats as recipients. The recipients in the experimental groups were treated with estrogen, 25?μg/kg every another day, by means of subcutaneous injection. After 16 weeks of treatment, renal function and the histological disorders of chronic rejection were studied. The infiltration of CD5 + and CD68 + cells and the expression of ICAM 1 and TGF β1 mRNA in the allografts were evaluated by using immunohistological staining and reverse transcription polymerase chain reaction respectively. Results Compared with control group, the 24 h urine protein in the experimental groups was markedly decreased ( 52.9 ± 19.0 ?vs 580.1 ± 226.3 ?mg/24?h, P < 0.01 ), serum creatitine level lowered ( 1.05 ± 0.02 ?vs 2.05 ± 0.31 ?mg/24?h, P < 0.01 ) and the creatitine clearance increased ( 0.32 ± 0.02 ?vs 0.13 ± 0.05 ?ml·min -1 ·100g -1 , P < 0.01 ). The infiltration of CD5 and CD68 positive cells, interstitial fibrosis, glomerular sclerosis and vascular intimal thickening in the allografts were alleviated in the experimental groups, in consistence with decreased expression of ICAM 1 and TGF β1 mRNA. Conclusions Estrogen can prevent chronic renal rejection and the influenced expression of above cytokins might be involved in the mechanisms. These results suggest that estrogen may be a drug potentially against chronic renal rejection.