Xia Anzhou, Li Yong, Li Na, Xue Zhi, Xia Jieyun, Wei Tiantian, Cao Jing
Department of Pharmacology, School of Pharmacy, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, Jiangsu Province, China,
Int Urol Nephrol. 2014 Jul;46(7):1455-64. doi: 10.1007/s11255-014-0748-4. Epub 2014 Jun 14.
Ischemic postconditioning is a procedure during which intermittent reperfusions are performed in the early phase of reperfusion to protect organs from ischemia/reperfusion injury. And in this study, we mainly investigated the injury-alleviative role of mitogen-activated protein kinase-activating protein kinase-2 (MAPKAPK-2) and heat shock protein 27 (HSP27) in renal ischemic reperfusion injury during the procedure of ischemic postconditioning.
Sprague-Dawley rats were randomly divided into four groups. The injury models were prepared by clipping the left renal pedicle of rats after ligating the right renal pedicle for 60 min. In the ischemic postconditioning group, sequential reperfusions were done for 10 s and another ischemia for 10 s for six cycles after kidney ischemia for 60 min. In addition, the specific inhibitor SB203580 was injected through caudal vein before ischemia. Serum creatinine, blood urea nitrogen and the expression of HSP27 and MAPKAPK-2 were detected 1, 3, 6 and 24 h later after reperfusion. Furthermore, phosphorylation of HSP27 and MAPKAPK-2 protein contents, histological changes and apoptosis were compared 24 h later after reperfusion.
Our data showed that ischemic postconditioning attenuated the renal dysfunction and cell apoptosis induced by I/R and increased phosphorylation of MAPKAPK-2 and HSP27. The results indicated that ischemic postconditioning decreased apoptosis and improved renal function.
Taken together, it is suggested that the renal protective effect may be related to the levels of HSP27 and MAPKAPK-2 activation.
缺血后处理是一种在再灌注早期进行间歇性再灌注以保护器官免受缺血/再灌注损伤的操作。在本研究中，我们主要探讨了丝裂原活化蛋白激酶激活蛋白激酶-2（MAPKAPK-2）和热休克蛋白27（HSP27）在缺血后处理过程中对肾缺血再灌注损伤的减轻作用。
将Sprague-Dawley大鼠随机分为四组。在结扎右侧肾蒂60分钟后夹闭左侧肾蒂制备损伤模型。在缺血后处理组中，肾缺血60分钟后，依次进行10秒的再灌注和10秒的缺血，共6个循环。此外，在缺血前经尾静脉注射特异性抑制剂SB203580。再灌注后1、3、6和24小时检测血清肌酐、血尿素氮以及HSP27和MAPKAPK-2的表达。此外，在再灌注24小时后比较HSP27和MAPKAPK-2蛋白含量的磷酸化、组织学变化和细胞凋亡情况。
我们的数据表明，缺血后处理减轻了I/R诱导的肾功能障碍和细胞凋亡，并增加了MAPKAPK-2和HSP27的磷酸化。结果表明，缺血后处理减少了细胞凋亡并改善了肾功能。
综上所述，提示肾脏保护作用可能与HSP27水平和MAPKAPK-2的激活有关。
