Williams P, Lopez H, Britt D, Chan C, Ezrin A, Hottendorf R
Glycomed Incorporated, Alameda, California, USA.
J Pharmacol Toxicol Methods. 1997 Feb;37(1):1-7. doi: 10.1016/s1056-8719(96)00141-4.
The purpose of this study was to characterize the time course of renal ischemia-reperfusion injury in the rat. Male Sprague-Dawley rats were subjected to bilateral renal clamping for 45 min. At reestablishment of blood flow, the rats were divided into nine groups (representing 0, 0.5, 1, 2, 4, 6, 9, and 24 h, and 1 week post-ischemia). At each time point, blood samples were taken for analysis of blood urea nitrogen (BUN) and creatinine, and both kidneys were harvested for histopathology and myeloperoxidase activity (MPO) assays. An intracellular adhesion molecular (ICAM-1) monoclonal antibody (IMAb) was tested in a separate group of animals (1 mg/rat) to confirm that it may provide renal protection previously reported by Kelly et al. (1994). Following renal ischemia, significant increases in serum BUN and creatinine were observed compared to levels in normal animals. Serum BUN and creatinine increased 2, 4, and 6 h post-ischemia leading to peak elevations 24 h post-ischemia. Values returned to normal at the 1 week time point. MPO activity was slightly increased 2 and 4 h following ischemia, with peak elevations occurring at the 6-h and 9-h time points. Histopathologic examination of kidneys revealed that the most severe damage occurred at the 24-h time point, which correlated with the peak elevations in serum BUN and creatinine. Evidence of renal injury was still evident histologically 1 week following ischemia, although renal function tests (BUN and creatinine) had returned to normal. In summary, renal injury following ischemia may be demonstrated as early as 4 h post-ischemia as judged by changes in renal function, MPO levels, and renal histopathology. However, based upon renal function tests and histology, peak injury is observed approximately 24 h following ischemia. The ICAM-1 monoclonal antibody, ICAM-Ab, provided some renal protection against ischemia-reperfusion injury in this study as measured by serum creatinine, BUN and renal histopathology. However, in contrast to the results reported by Kelly et al., the magnitude of the protective effects was not as dramatic in the present study, and furthermore, no reductions in renal MPO activity were observed.
本研究的目的是描述大鼠肾缺血-再灌注损伤的时间进程。雄性Sprague-Dawley大鼠双侧肾蒂夹闭45分钟。恢复血流后，将大鼠分为九组（分别代表缺血后0、0.5、1、2、4、6、9、24小时以及1周）。在每个时间点采集血样以分析血尿素氮（BUN）和肌酐，并摘取双侧肾脏进行组织病理学检查和髓过氧化物酶活性（MPO）测定。在另一组动物（1mg/大鼠）中测试了细胞间黏附分子（ICAM-1）单克隆抗体（IMAb），以证实其可能提供如Kelly等人（1994年）先前报道的肾脏保护作用。肾缺血后，与正常动物相比，血清BUN和肌酐显著升高。缺血后2、4和6小时血清BUN和肌酐升高，在缺血后24小时达到峰值升高。在1周时间点时数值恢复正常。缺血后2和4小时MPO活性略有增加，在6小时和9小时时间点达到峰值升高。肾脏组织病理学检查显示，最严重的损伤发生在24小时时间点，这与血清BUN和肌酐的峰值升高相关。尽管肾功能测试（BUN和肌酐）已恢复正常，但缺血1周后肾脏损伤的组织学证据仍然明显。总之，根据肾功能、MPO水平和肾脏组织病理学变化判断，缺血后最早在4小时即可出现肾损伤。然而，根据肾功能测试和组织学检查，缺血后约24小时观察到损伤峰值。通过血清肌酐、BUN和肾脏组织病理学测量，ICAM-1单克隆抗体ICAM-Ab在本研究中提供了一定的肾脏保护作用，使其免受缺血-再灌注损伤。然而，与Kelly等人报道的结果相反，本研究中保护作用的程度没有那么显著，而且，未观察到肾脏MPO活性降低。
