Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
J Surg Res. 2011 Jul;169(1):e77-84. doi: 10.1016/j.jss.2011.02.021. Epub 2011 Apr 13.
Ischemia/reperfusion injury (IRI) has a negative effect on renal allograft survival. Using a rat model of kidney IRI in this study, we investigated the overall effect of selective c-Jun N-terminal kinase (JNK) inhibitor SP600125 on renal IRI events.
All 45 Fisher rats were anesthetized and renal IRI model was established by 45 min clamp of bilateral renal pedicles and 24 h reperfusion. Vehicle solution or SP600125 solution was intraperitoneally injected 45 min before ischemia, respectively. Analysis of renal histology, function, reactive oxygen species (ROS) expression, JNK phosphorylation status, as well as intra-renal pro-inflammatory cytokines expression was evaluated in this study.
After IRI, the levels of blood urea nitrogen, creatinine, tissue malondialdehyde, TNF-α, IL-1β, IL-6 were all elevated significantly, while superoxide dismutase, catalase activity were decreased. Histologic findings showed severe devastating lesions and increased rodent cell apoptosis; SP600125 effectively improved morphologic features, reversed above-mentioned parameters, and significantly attenuated c-Jun phosphorylation, as well as intra-renal pro-inflammatory cytokines expression compared with vehicle-treated group.
These data demonstrate that inhibition of c-Jun with SP600125 is capable of attenuating renal IRI, which might be a novel therapy target.
缺血/再灌注损伤（IRI）对肾移植的存活有负面影响。本研究通过建立大鼠肾脏 IRI 模型，研究了选择性 c-Jun N-末端激酶（JNK）抑制剂 SP600125 对肾脏 IRI 事件的整体影响。
所有 45 只 Fisher 大鼠麻醉后，通过夹闭双侧肾蒂 45 分钟和再灌注 24 小时建立肾 IRI 模型。缺血前 45 分钟分别腹腔注射载体溶液或 SP600125 溶液。本研究评估了肾组织学、功能、活性氧（ROS）表达、JNK 磷酸化状态以及肾内促炎细胞因子表达的变化。
IRI 后，血尿素氮、肌酐、组织丙二醛、TNF-α、IL-1β、IL-6 水平均显著升高，超氧化物歧化酶、过氧化氢酶活性降低。组织学检查显示严重的破坏性病变和增加的啮齿动物细胞凋亡；与载体处理组相比，SP600125 可有效改善形态特征，逆转上述参数，并显著减弱 c-Jun 磷酸化和肾内促炎细胞因子表达。
这些数据表明，用 SP600125 抑制 c-Jun 能够减轻肾 IRI，这可能是一种新的治疗靶点。
