Brom H L, van Breda Vriesman P J, Terpstra J L
Kidney Int. 1982 Feb;21(2):323-9. doi: 10.1038/ki.1982.25.
Donor pretreatment of 100 mg/kg each of cyclophosphamide (CY) and methylprednisolone (P) infused 5 hours before nephrectomy invariably prolongs the survival of DLA mismatched, MLC incompatible nonlittermate Beagle renal allografts as well as the survival of mongrel renal allografts. The effect of donor pretreatment appears to be mediated by cyclophosphamide and its metabolites because methylprednisolone pretreatment does not significantly prolong survival. Methylprednisolone is needed, however, because it abolishes cyclophosphamide pretreatment mediated early but transient postoperative renal (allograft) insufficiency. The effect of donor pretreatment appears to be mediated by drugs residing in the graft; mannitol infusions given 1 hour prior to donor nephrectomy or peroperatively into the recipient decrease the renal cortical content of carbon 14 cyclophosphamide and its metabolites and abolishes the prolonged survival. Because donor pretreated kidneys contain less than 0.5% of the infused dose of carbon 14 cyclophosphamide, the drugs appear to exert their effect locally in the transplanted kidney. Donor pretreatment mediating prolonged canine renal allograft survival appears to be an example of influencing a biological process by a localized drug delivery by virtue of unique properties of the drug and because early postoperatively host sensitization occurs mainly at the site of the graft.
在肾切除术前5小时给供体分别注射100mg/kg的环磷酰胺（CY）和甲基泼尼松龙（P），总能延长DLA不匹配、MLC不相容的非同窝比格犬肾移植以及杂种犬肾移植的存活时间。供体预处理的效果似乎是由环磷酰胺及其代谢产物介导的，因为甲基泼尼松龙预处理并不能显著延长存活时间。然而，需要甲基泼尼松龙，因为它能消除环磷酰胺预处理介导的早期但短暂的术后肾（同种异体移植）功能不全。供体预处理的效果似乎是由移植器官中的药物介导的；在供体肾切除术前1小时或术中给受体输注甘露醇，会降低肾皮质中碳14环磷酰胺及其代谢产物的含量，并消除存活时间的延长。由于供体预处理的肾脏中碳14环磷酰胺的注入剂量不到0.5%，这些药物似乎在移植肾中局部发挥作用。供体预处理介导犬肾移植存活时间延长似乎是一个通过药物的独特性质进行局部给药来影响生物学过程的例子，因为术后早期宿主致敏主要发生在移植部位。
