抑制一氧化氮合酶/一氧化氮表达与减轻移植肾排斥反应

Relationship between Inhibited Expression of Nitric Oxide Synthase/Nitric Oxide and Alleviation of Renal Allograft Rejection in Rats

目的探讨氨基胍和骨化三醇联合抑制诱导型一氧化氮合酶/一氧化氮(iNOS/NO)表达与减轻肾移植急性排斥反应之间的关系。方法以健康雄性Wistar大鼠和SD大鼠作为供、受体建立肾移植模型。实验随机分为5组:I组为同基因移植组,II组为急性排斥对照组,III组为氨基胍治疗组,IV组为骨化三醇治疗组,V组为联合用药组;观察各组受鼠生存期和移植后5d肾组织病理学变化,检测血肌酐(Cr)、尿素氮(BUN)及肾组织匀浆中iNOS/NO的变化。结果I～V组受者存活时间分别为(9.1±1.9)d、(5.3±0.8)d、(9.7±2.1)d、(8.6±1.6)d和(12.9±3.4)d。III、IV组受者存活期、肾功能、移植肾排斥反应程度及肾组织iNOS/NO表达水平较II组明显改善或降低(P<0.05);V组效果更佳(P<0.05),但对进一步减轻排斥反应无统计学意义(P>0.05)。结论氨基胍和骨化三醇联用对减少移植肾iNOS/NO的表达有正协同作用,但不能进一步减轻排斥反应。

Objective To explore the relationship between inhibited expression of inducible nitric oxide synthase/nitric oxide and lessening of acute renal allograft rejection in rats. Methods Orthotopic renal transplantation from Wistar rats to SD rats was used as a model of study. The experimental rats were divided into the following groups： Group Ⅰ and Ⅱ as allotransplantation control group and acute rejection control group, respectively. Group Ⅲ, Ⅳ and Ⅴ were treated with aminoguanidine （AG）, calcitriol and the combined use of calcitriol and AG, respectively. The survival time of recipients was observed. 5 days after operation, concentrations of serum Cr and BUN and expression of iNOS and NO in allograft homogenate were measured, morphological changes of the allograft were evaluated by histological examination. Results The recipient survival time in the groupsⅠ-Ⅴ were 9.1±1.9 d, 5.3±0.8 d, 9.7±2.1 d, 8.6±1.6 d and 12.9±3.4 d, respectively. The recipient survival time, renal function, degree of acute renal allograft rejection and expression of iNOS and NO in allograft were significantly improved or decreased in group Ⅲ, Ⅳ in comparison with group Ⅱ （ P 〈 0.05）. The results of group Ⅴ were better than those of group Ⅲ and group Ⅳ （P 〈 0.05）, but no significant improvement for further reduction of allograft rejection （P 〉 0.05）. Conclusion Combined use AG and calcitriol has a synergistic effect to reduce expression of iNOS and NO in renal allograft, but it can not further alleviate the allograft rejection.