供体应用钙调磷酸酶抑制剂预处理减少大鼠肾移植缺血再灌注损伤及机制

Using Calcineurin Inhibitor in donor preconditioning reduce ischemia-reperfusion injury in rat renel transplantation and the mechanisms

目的缺血性预处理被证实能够提高器官对缺血再灌注损伤的耐受性,在肾移植领域具有较大的应用价值。但因其实施过程中还具有一系列问题从而限制了这一技术的临床应用。因此笔者提出使用药物钙调磷酸酶抑制剂(CNIs)对供体进行预处理,以期减少移植后缺血再灌注损伤。方法采用近交系Lewis大鼠肾移植模型,设置环孢素A组(CsA,10 mg/kg)、他克莫司组(Tac,1 mg/kg)、生理盐水对照组。通过比较肾移植后第3天各实验组与对照组移植肾功能(血清肌酐)、组织病理学改变,以及移植肾组织中肿瘤坏死因子α(TNF-α)、热休克蛋白70(HSP-70)的表达水平,评估移植肾缺血再灌注损伤程度并探讨其发生机制。结果各实验组血清肌酐值均小于对照组,组织病理学改变优于对照组,TNF-α表达水平低于对照组,HSP-70水平高于对照组。结论钙调磷酸酶抑制剂供体预处理能降低移植肾组织TNF-α,增加HSP-70的表达,从而减少肾移植缺血再灌注损伤。

Objective Ischemic preconditioning confirmed that can improve the tolerability of organs when the ischemic reperfusion injury happened, but the process also had a series of problems so as to limit the technology using in clinical. There was to use calcineurin inhibitors pretreatment to the donor for researching to reduce ischemia-reperfusion injury. Methods Lewis rat transplant models was divided into 3 groups： Cyclosporine A group （CsA, 10 mg/kg）, Tacrolimus group （Tac, 1 mg/kg）; Placebo control group （saline）. The graft function （serum creatinine）, histopathological changes, and renal al- lograft tissue TNF-α, HSP-70 expression level of each observation group were compared with control group when third day post-transplants. Allograft ischemia-reperfusion injury was evaluated and it＇s mechanism was discussed. Results Serum creatinine of CsA group and Tac group were lower than that of vehicle group. Histopathology change of CsA group and Tac group were better than that of vehicle group. TNF-αdevel of CsA group and Tac group was lower than the Placebo control group. HSP-70 level of CsA group and Tac group were higher than that of Placebo control group. Conclusion Calcineurin inhibitor donor pretreatment can reduce ischemia-reperfusion injury. Its mechanism may reduce TNF-αdevel and increase HSP-70 expression in allograft.