Chrupcala M, Pomer S, Waldherr R, Staehler G, Kirschfink M
Chirurgische Klinik, Städtische Kliniken Dortmund.
Urologe A. 1996 Nov;35(6):478-84. doi: 10.1007/s001200050056.
In this study a modified experimental kidney xenograft model was developed, which reproduced, in a reliable way, the course of hyperacute rejection. In this model guinea-pig kidneys were transplanted to rats using end-to-side anastomoses with recipient aorta and vena cava, respectively, and ureter drainage for diuresis monitoring. The aim of this study was to investigate the protective effects of complement modulation by soluble complement receptor 1 (sCR1) on the xenografts. Twenty-four xenotransplantations were performed and recipients randomized for treatment either by 3 ml saline or 50 mg/kg sCR1 as a 3-ml bolus. It was found that sCR1 was highly efficient in delaying hyperacute rejection from 10.5 +/- 2.1 min in the control group to at least 2 h in the therapy group and in prolongation of graft function. The complement activity was significantly reduced in the sCR1-treated rats, even at the time of rejection, as a result of complement modulation in this group of xenograft recipients. Xenografts from saline-treated animals showed necroses, interstitial haemorrhages and platelet aggregates occluding the vessels as soon as 10 min after the reperfusion started. No such changes could be seen even after 120 min in the xenografted kidneys of sCR1-treated rats. Also C3 deposits in the glomeruli and interstitium were markedly reduced.
在本研究中,开发了一种改良的实验性肾异种移植模型,该模型以可靠的方式再现了超急性排斥反应的过程。在该模型中,将豚鼠肾脏分别通过端侧吻合术移植到大鼠的主动脉和腔静脉,并通过输尿管引流来监测利尿情况。本研究的目的是研究可溶性补体受体1(sCR1)调节补体对异种移植物的保护作用。进行了24次异种移植,并将受体随机分为两组,分别给予3 ml生理盐水或50 mg/kg sCR1(3 ml推注)进行治疗。结果发现,sCR1能高效延迟超急性排斥反应,将对照组的排斥反应时间从10.5±2.1分钟至少延长至治疗组的2小时,并延长移植物功能。由于对这组异种移植受体进行了补体调节,sCR1治疗的大鼠即使在排斥反应发生时,补体活性也显著降低。生理盐水处理动物的异种移植物在再灌注开始后10分钟就出现了坏死、间质出血和血小板聚集阻塞血管的情况。而sCR1治疗的大鼠异种移植肾脏即使在120分钟后也未见此类变化。此外,肾小球和间质中的C3沉积也明显减少。