Schneeberger H, Schleibner S, Illner W D, Messmer K, Land W
Department of Surgery, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Germany.
Clin Transpl. 1993:219-32.
In a prospective, randomized, double-blind, placebo-controlled trial, rhSOD was given to cadaveric renal allograft recipients intravenously in a dose of 200 mg during surgery, and its effect on both acute and chronic rejection was investigated. The results showed that rhSOD exerts a beneficial effect on acute rejection episodes as indicated by a statistically significant reduction of first acute rejection episodes to 18.5% compared with 33.3% in controls, and a reduction in early irreversible acute rejection to 3.7% compared with 12.5% in controls. With regard to longterm results, there was a statistically significant improvement in the actual 5-year graft survival rate for rhSOD-treated patients to 68% (with a corresponding 13-year half-life) compared with 50% in controls (with a corresponding 6-year half-life). The incidence of acute rejection episodes did not prove to be a risk factor for long-term graft outcome. Rather only the combination of acute rejection episodes and the presence of uninfluenced reperfusion injury appeared to have a detrimental effect on long-term prognosis. The beneficial effect of rhSOD observed in this trial is not well understood, although one can assume that the effect is brought about by interference of rhSOD with ischemia or reperfusion injury to the allograft by oxygen-free radicals. In this sense, rhSOD may mitigate increased MHC expression and presentation, cytokine-adhesion molecule expression, and APC activation induced by reperfusion injury. In addition, in accordance with the "response-to-injury" hypothesis to explain the pathogenesis of arteriosclerosis, rhSOD may mitigate acceleration of chronic obliterative rejection or arterio-/arteriolosclerosis induced by reperfusion injury. In this sense, rhSOD may act indirectly by reducing acute rejection-mediated endothelial injury, or directly, by ablation of reperfusion-mediated acute endothelial injury.
在一项前瞻性、随机、双盲、安慰剂对照试验中，在手术期间给尸体肾移植受者静脉注射剂量为200mg的重组人超氧化物歧化酶（rhSOD），并研究其对急性和慢性排斥反应的影响。结果显示，rhSOD对急性排斥反应发作具有有益作用，首次急性排斥反应发作的发生率在统计学上显著降低至18.5%，而对照组为33.3%；早期不可逆急性排斥反应降低至3.7%，而对照组为12.5%。关于长期结果，rhSOD治疗患者的实际5年移植存活率在统计学上有显著提高，达到68%（相应的半衰期为13年），而对照组为50%（相应的半衰期为6年）。急性排斥反应发作的发生率并未被证明是长期移植结果的危险因素。相反，只有急性排斥反应发作与未受影响的再灌注损伤同时存在似乎对长期预后有不利影响。尽管可以假设rhSOD的作用是通过其对同种异体移植物的缺血或再灌注损伤的自由基干扰来实现的，但在该试验中观察到的rhSOD的有益作用尚不完全清楚。从这个意义上说，rhSOD可能减轻再灌注损伤诱导的主要组织相容性复合体（MHC）表达和呈递增加、细胞因子-黏附分子表达以及抗原呈递细胞（APC）激活。此外，根据解释动脉粥样硬化发病机制的“损伤反应”假说，rhSOD可能减轻再灌注损伤诱导的慢性闭塞性排斥反应或动脉/小动脉硬化的加速。从这个意义上说，rhSOD可能通过减少急性排斥反应介导的内皮损伤间接起作用，或者通过消除再灌注介导的急性内皮损伤直接起作用。
