论文部分内容阅读
目的探讨FTY720对大鼠肾脏在缺血再灌注损伤中的保护作用及对缺氧诱导因子1α(HIF1α)表达水平的影响。方法将125只健康雄性SD大鼠随机平均分为5组。建立大鼠肾脏缺血再灌注模型。FTY720组:缺血再灌注前3d连续用FTY7201mg·kg-1·d-1灌胃;霉酚酸酯(MMF)组:缺血再灌注前3d连续用MMF20mg·kg-1·d-1灌胃;环孢素A(CsA)组:缺血再灌注前3d连续用CsA10mg·kg-1·d-1颈部皮下注射;对照组:术前不给予任何处理;假手术组:不建立肾脏缺血再灌注损伤模型。观察各组大鼠术后0、6、24、72h及7d时的血肌酐水平以及肾组织中HIF1αmRNA和蛋白表达水平。结果(1)大鼠肾脏缺血再灌注后各时间点的血清肌酐值水平均高于假手术组(P<0.05)。但是FTY720组再灌注6、24和72h时血肌酐值明显低于对照组,差异有统计学意义(P<0.05)。而MMF组、CsA组各时间点与对照组比较,差异无统计学意义。(2)再灌注后0、6和24h,FTY720组肾组织中HIF1αmRNA和蛋白水平明显高于同期对照组(P<0.05),而MMF组和CsA组与对照组相比较,差异无统计学意义。结论FTY720可诱导肾脏缺血再灌注早期HIF1αmRNA的快速转录和蛋白表达量的增加,这可能是减轻肾脏缺血再灌注损伤的重要机理之一。
Objective To investigate the protective effect of FTY720 on renal ischemia-reperfusion injury and its effect on the expression of hypoxia inducible factor-1α (HIF1α) in rats. Methods 125 healthy male SD rats were randomly divided into five groups. Rat renal ischemia-reperfusion model was established. FTY720 group: 3 days before ischemia reperfusion with FTY7201mg · kg-1 · d-1 intragastric administration; mycophenolate mofetil (MMF) group: 3 days before ischemia-reperfusion with MMF20mg · kg-1 · d- The CsA group was injected subcutaneously with CsA10mg · kg-1 · d-1 for 3 days before ischemia-reperfusion. The control group: no treatment was given before the operation. The sham operation group: the kidney was not established Ischemia-reperfusion injury model. The levels of serum creatinine and the expression of HIF1αmRNA and protein in renal tissues were observed at 0, 6, 24, 72h and 7d after operation. Results (1) Serum creatinine levels at various time points after renal ischemia-reperfusion in rats were significantly higher than those in sham operation group (P <0.05). However, the serum creatinine values in FTY720 group at 6, 24 and 72h after reperfusion were significantly lower than those in control group (P <0.05). The MMF group, CsA group at each time point compared with the control group, the difference was not statistically significant. (2) At 0, 6 and 24 h after reperfusion, the levels of HIF1αmRNA and protein in the kidney tissue of FTY720 group were significantly higher than those of the control group (P <0.05), while there was no significant difference between MMF group and CsA group . Conclusion FTY720 can induce the rapid transcription and protein expression of HIF1α mRNA in the early stage of renal ischemia / reperfusion, which may be one of the important mechanisms to reduce renal ischemia-reperfusion injury.