Department of Urology, Changzheng Hospital, The Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, People's Republic of China.
Inflammation. 2012 Feb;35(1):122-9. doi: 10.1007/s10753-011-9296-6.
Renal grafts from brain-dead donors compared to living donors have a significantly shortened survival time due to heightened renal immunogenicity. The influence of pretreatment with a JNK signal transduction inhibitor on ischemia-reperfusion injury was examined in a renal transplant model using donors from a standardized rat model of brain death. Donors were treated immediately after induction of brain death with a JNK signal transduction inhibitor or saline. Kidney grafts from experimental group and control groups (saline-treated brain dead or living donor grafts) were examined serially up to 7 days post transplantation by morphology, immunohistology, and real-time PCR. JNK inhibition reduced the intensity of ischemia-reperfusion injury and acute rejection compared to saline treated donors. Likewise, cellular infiltration, mRNA transcription of some representative proinflammatory mediators and MHC-II molecules in the grafts were diminished in the JNK-inhibited donors compared to saline controls. Lewis rats transplanted with kidneys from JNK inhibited, brain-dead BN donors survived significantly longer than rats transplanted with saline treated brain-dead donors. The JNK inhibitor pretreatment of brain dead rats improved donor kidney quality, and improved graft survival.
由于肾脏免疫原性增强，脑死亡供体的肾移植物与活体供体相比，存活时间明显缩短。本研究使用脑死亡标准化大鼠模型中的供体，在肾移植模型中观察了预先应用 JNK 信号转导抑制剂对缺血再灌注损伤的影响。供体在脑死亡诱导后立即用 JNK 信号转导抑制剂或生理盐水处理。实验组和对照组（用生理盐水处理的脑死亡或活体供体移植物）的肾脏移植物在移植后 7 天内通过形态学、免疫组织化学和实时 PCR 进行连续检查。与生理盐水处理的供体相比，JNK 抑制可降低缺血再灌注损伤和急性排斥反应的强度。同样，在 JNK 抑制的供体中，与生理盐水对照组相比，一些代表性促炎介质和 MHC-II 分子的细胞浸润和 mRNA 转录减少。与用生理盐水处理的脑死亡供体移植的大鼠相比，用 JNK 抑制的 BN 脑死亡供体肾脏移植的 Lewis 大鼠存活时间明显更长。脑死亡大鼠预先应用 JNK 抑制剂可改善供体肾脏质量，并延长移植物存活时间。
