小鼠缺血预处理激酶：一种部分表征肾再灌注和保存损伤的强大工具。
Mouse IPK: A Powerful Tool to Partially Characterize Renal Reperfusion and Preservation Injury.
作者信息
Lindell Susanne L, Williams Natascha, Brusilovsky Ilia, Mangino Martin J
机构信息
Department of Surgery, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA 232980, USA ; Department of Anesthesiology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA 232980, USA.
Department of Surgery, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA 232980, USA.
出版信息
Open Transplant J. 2011 Jan 1;5:15-22. doi: 10.2174/1874418401105010015.
MAIN PROBLEM
The molecular basis of renal preservation injury is not well understood. Since mouse kidney transplantation models are not useful in this setting, a mouse Isolated Perfused Kidney (IPK) model was developed to take advantage of mouse genetic design capabilities for testing complex biological hypothesis regarding mechanisms of preservation injury in transplanted kidneys.
METHODS
Mouse kidneys were recovered, preserved, and reperfused in-vitro with an acellular physiological crystalloid buffer containing hypo-physiological oncotic pressure. Outcome variables were measured to predict preservation injury. These included perfusate flow, vascular resistance, VO, urine output, GFR, proteinuria, LDH release, and edema. The model was tested by subjecting mouse kidneys to cold storage in University of Wisconsin (UW) solution for 24, 48, or 72 hours (time-dependent preservation injury), cold storage in Euro-Collins Solution (solution dependent preservation injury), and exposure to prior warm ischemia (DCD dependent preservation injury).
RESULTS
The model accurately predicted the qualitative and quantitative changes in the readouts based on known responses to preservation injury in kidney transplants in large animals and humans.
CONCLUSION
The mouse IPK accurately predicts many of the variables associated with renal organ preservation injury in the very early phases of reperfusion and may provide an attractive model for studying the molecular basis of renal preservation injury.
主要问题
肾脏保存损伤的分子基础尚未完全明确。由于小鼠肾脏移植模型在此情况下并不适用，因此开发了一种小鼠离体灌注肾（IPK）模型，以利用小鼠的基因设计能力来测试关于移植肾保存损伤机制的复杂生物学假设。
方法
回收小鼠肾脏，在体外使用含有低生理胶体渗透压的无细胞生理性晶体缓冲液进行保存和再灌注。测量结果变量以预测保存损伤。这些变量包括灌注液流量、血管阻力、VO、尿量、肾小球滤过率、蛋白尿、乳酸脱氢酶释放和水肿。通过将小鼠肾脏置于威斯康星大学（UW）溶液中冷藏24、48或72小时（时间依赖性保存损伤）、置于欧洲柯林斯溶液中冷藏（溶液依赖性保存损伤）以及暴露于先前的热缺血（心脏死亡供体依赖性保存损伤）来测试该模型。
结果
该模型基于在大型动物和人类肾脏移植中对保存损伤的已知反应，准确预测了读数的定性和定量变化。
结论
小鼠IPK在再灌注的早期阶段准确预测了许多与肾脏器官保存损伤相关的变量，可能为研究肾脏保存损伤的分子基础提供一个有吸引力的模型。
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