肾脏缺血晚期预适应对肾功能保护机制的研究

Investigation of renal function prevention by kidney ischemic preconditioning.

目的研究肾脏晚期缺血预适应(ischemic preconditioning,IPC)的存在和探讨肾第二保护窗现象(second window of ischemic preconditioning,SWOP)的分子机制以及药物性预适应对肾缺血性损伤的保护作用。方法制备大鼠缺血性急性肾功能衰竭(ARF)模型,测定血HSP70,iNOS,ICAM-1 mRNA水平,抽取静脉血测定血肌酐,尿素氮水平,用电镜,光镜等仪器观察肾病理变化,并以药物预适应后观察上述指标改变。结果(1)缺血性ARF模型予缺血预适应干预后其HSP70、iNOS mRNA的表达水平显著升高,而其ICAM-1等细胞因子则降低。(2)KATP通道阻滞剂、腺苷受体A1阻滞剂、PKC阻滞剂能消除IPC对缺血再灌注(ischemia reperfusion,IR)的保护作用致血肌酐、尿素氮水平升高,而KATP激动剂、腺苷受体A1激动剂、PKC激动剂起反作用。结论(1)在缺血性ARF模型中,晚期IPC能显著降低肾缺血再灌注损伤时肌酐和尿素氮水平,改善肾功能。(2)腺苷受体激动剂、KATP通道激动剂、PKC激动剂能诱导IPC对IR损伤组织的保护作用。

Objective To investigate the existence of the second window of renal ischemic preconditioning（SWOP）and illustrate the molecule mechanism of SWOP and drug preconding preventing the post-ischemic injury.Methods Mouse animal model of ischemic acute renal failure（ARF） was performed.The mRNA expression of HSP70,ICAM-1,iNOS,blood creatine and urine nitrogen were detected to evaluate the renal function,and the pathology change were evaluated by microscopy.Results（1）The expression of HSP70,iNOS mRNA in kidney after IPC were increased and the expression of ICAM-1 was decreased.（2）The preventive effect on the post-ischemia injury were decreased by theopheny and chelerythrire.Conclusion（1）The existence in the second window of protection of renal ischemic reconditioning was detected by this rescuer.It can decrease the injury of ischemia reperfusion.（2）Bimakalim and snglycerol can protect the renal tissues of IPC.