去氧精胍菌素对犬肾移植中血管排斥反应的影响。

Effect of deoxyspergualin on vascular rejection in canine kidney transplantation.

作者信息

Tanabe K, Takahashi K, Nemoto K, Okada M, Yasuo M, Hayasaka Y, Toma H, Ota K

机构信息

Department of Urology, Tokyo Women's Medical College, Japan.

出版信息

J Urol. 1994 Aug;152(2 Pt 1):562-6. doi: 10.1016/s0022-5347(17)32793-3.

DOI:10.1016/s0022-5347(17)32793-3

PMID:8015112

Abstract

Deoxyspergualin (DSG), an analogue of spergualin produced by Bacillus laterosporus, has a strong immunosuppressive effect in various transplantation models. In this study, we investigated the effect of DSG on vascular rejection in canine kidney transplantation. To enhance vascular rejection, donor-specific blood transfusion (DST) was carried out on days 28, 21 and 14 preceding kidney transplantation. After DST, the donor kidney was transplanted to the recipient iliac fossa. The recipient animals were divided into five groups: namely, Group 1 (n = 7), no treatment; Group 2 (n = 6), DST only; Group 3 (n = 5), DSG only (treated with DSG intravenously at 1.2 mg./kg./day for the first 3 days after transplantation, 1.0 mg./kg./day for the following 3 days and 0.8 mg./kg./day for the following 8 days); Group 4 (n = 6), DST and DSG treatment (same protocol as Group 3); and Group 5 (n = 5), DST and cyclosporine (CsA) (treated with CsA orally at 10 mg./kg./day for 14 days after transplantation). In Group 2, DST treatment significantly reduced kidney graft survival time (8.6 +/- 2.2 days) compared with Group 1 (14.1 +/- 5.5 days). Despite DST, DSG treatment (Group 4) significantly prolonged graft survival time (29.5 +/- 2.6 days), whereas treatment with CsA (Group 5) did not prolong survival time (14.1 +/- 5.5 days) (Group 4 versus 5, p < 0.01). The onset of rejection was significantly delayed in Group 4 (22.1 +/- 2.7 days) compared with Groups 2 (5.7 +/- 2.4 days) and 5 (13.0 +/- 5.7 days) (p < 0.01). In contrast, the interval between rejection onset and animal death was significantly reduced in Groups 2 (3.0 +/- 0.6 days) and 5 (2.4 +/- 1.0 days) compared with Group 4 (7.3 +/- 1.7 days) (p < 0.01). These findings suggest that DSG successfully prevented humoral-type (accelerated acute-type) rejections. Histologically, nonDST groups (Groups 1 and 3) showed minimum vascular rejection. In contrast, all recipients in Group 2 showed severe vascular rejection, as did 80% of CsA treated-animals (Group 5). Despite DST, however, 84% of DSG treated-animals (Group 4) showed minimal or mild vascular rejection and only 17% had severe rejection (Group 4 versus 5, p < 0.04). These data suggest that both clinically and histologically, DSG has more potent immunosuppressive effects against humoral and vascular rejection than CsA.

摘要

去氧精胍菌素（DSG）是由侧孢芽孢杆菌产生的精胍菌素类似物，在各种移植模型中具有强大的免疫抑制作用。在本研究中，我们调查了DSG对犬肾移植血管排斥反应的影响。为增强血管排斥反应，在肾移植前第28、21和14天进行供体特异性输血（DST）。DST后，将供体肾移植到受体髂窝。受体动物分为五组：即第1组（n = 7），不治疗；第2组（n = 6），仅DST；第3组（n = 5），仅DSG（移植后前3天静脉注射DSG，剂量为1.2mg/kg/天，接下来3天为1.0mg/kg/天，再接下来8天为0.8mg/kg/天）；第4组（n = 6），DST和DSG治疗（方案与第3组相同）；第5组（n = 5），DST和环孢素（CsA）（移植后14天口服CsA，剂量为10mg/kg/天）。在第2组中，与第1组（14.1±5.5天）相比，DST治疗显著缩短了肾移植存活时间（8.6±2.2天）。尽管进行了DST，但DSG治疗（第4组）显著延长了移植存活时间（29.5±2.6天），而CsA治疗（第5组）并未延长存活时间（14.1±5.5天）（第4组与第5组比较，p<0.01）。与第2组（5.7±2.4天）和第5组（13.0±5.7天）相比，第4组排斥反应的发生明显延迟（22.1±2.7天）（p<0.01）。相反，与第4组（7.3±1.7天）相比，第2组（3.0±0.6天）和第(组5)（2.4±1.0天）排斥反应发生至动物死亡的间隔显著缩短（p<0.01）。这些发现表明，DSG成功预防了体液型（加速急性型）排斥反应。组织学上，非DST组（第1组和第3组）显示出最小程度的血管排斥反应。相反，第2组的所有受体均表现出严重的血管排斥反应，CsA治疗的动物（第5组）中80%也是如此。然而，尽管进行了DST，但DSG治疗的动物（第4组）中84%表现出最小程度或轻度的血管排斥反应，只有17%有严重排斥反应（第4组与第5组比较，p<0.04）。这些数据表明，无论在临床还是组织学方面，DSG对体液和血管排斥反应的免疫抑制作用都比CsA更强。