BMP-7/Smad1/5/8信号通路在肾缺血后处理减轻大鼠肾缺血再灌注损伤中的作用  

Activation of BMP-7/Smad1/5/8 Signaling Pathway Contributes to the Protective Effect of Ischemic Postconditioning on Renal Ischemia-Reperfusion Injury in Rats

作　　者：张舒 李然 徐先知 黄元宏 夏安周 ZHANG Shu;LI Ran;XU Xianzhi;HUANG Yuanhong;XIA Anzhou(Department of Pharmacology,Xuzhou Medical University,Xuzhou,Jiangsu,221004)

机构地区：[1]徐州医科大学药理学教研室,徐州221004

出　　处：《药学与临床研究》2021年第1期7-11,共5页Pharmaceutical and Clinical Research

基　　金：江苏省高等学校大学生创新训练项目(20181013009Z);徐州市科技发展基金(XF10C072)。

摘　　要：目的:观察肾缺血后处理后BMP-7/Smad1/5/8信号通路活性改变,探讨肾缺血后处理减轻肾缺血再灌注损伤(IRI)的机制。方法:将雄性SD大鼠随机分为假手术组(sham组),缺血再灌注组(IR组),缺血后处理组(IPostC组)。各组又分成再灌注1.5、3、6、12、24 h共五个时间点亚组,每组6只大鼠。IR组采用结扎左侧肾蒂60 min后松开动脉夹、制备肾脏缺血再灌注损伤模型;IPostC组操作同IR组,恢复灌注前给予6个循环10 s再灌注/10 s缺血处理,然后恢复灌注。测定血肌酐(SCr)、尿素氮(BUN)浓度;免疫印迹法测定肾组织中BMP-7、USAG-1和p-Smad1/5/8蛋白的表达变化;TUNEL法分析肾小管上皮细胞凋亡情况。结果:与sham组相比,IR组各时间点SCr和BUN含量、USAG-1表达水平以及TUNEL凋亡指数(AI)明显增高,而BMP-7和p-Smad1/5/8蛋白表达水平显著下调,差异均具有统计学意义(P<0.05);与IR组各对应时间点相比,IPostC组SCr和BUN含量、USAG-1表达水平以及AI明显降低,而BMP-7和p-Smad1/5/8蛋白表达水平显著上调,差异具有统计学意义(P<0.05)。结论:肾IPostC对大鼠肾缺血再灌注损伤有一定的保护作用,其机制可能与上调BMP-7的表达、下调USAG-1的表达,继而激活BMP-7/Smad1/5/8信号通路以及抑制细胞凋亡有关。Objective:To observe the changes of BMP-7/Smad1/5/8 signaling pathway activity after renal ischemic postconditioning(IPostC),and to investigate the mechanism of IPostC in relieving renal ischemia reperfusion injury(IRI).Methods:Male SD rats were randomly divided into 3 groups:sham operation group(sham group);ischemia-reperfusion group(IR group);and ischemic postconditioning group(IPostC group).Each group was further divided into five time sub-groups according to different time points after reperfusion(1.5 h,3 h,6 h,12 h and 24 h),with 6 animals in each group.In the IR group,the renal IRI model was established by releasing the arterial clamps after ligating the left renal pedicle for 60 min.In the IPostC group,the operation was the same as that in the IR group,while six cycles of 10 s reperfusion/10 s ischemia were performed before the restoration of perfusion.Serum creatinine(SCr)and blood urea nitrogen(BUN)concentrations were measured.The expression of BMP-7,USAG-1 and p-Smad1/5/8 in renal tissues was determined by Western blot.Apoptosis of renal tubular epithelial cells was detected by TUNEL staining.Results:Compared with the sham group,the SCr and BUN concentrations,the USAG-1 expressions,and the apoptotic index(AI)were significantly increased at each time point in the IR group,with significant reductions of BMP-7 and p-Smad1/5/8(P<0.05);Compared with the IR group,the IPostC group resulted in significant increase of BMP-7 and p-Smad1/5/8 expression,and significant reduction of SCr and BUN concentrations,USAG-1 expression and AI(P<0.05).Conclusions:Renal IPostC has a protective effect on renal IRI in rats.The mechanism may be related to up-regulation of BMP-7 expression,down-regulation of USAG-1 expression,and subsequent activation of BMP-7/Smad1/5/8 signaling pathway and inhibition of apoptosis.

关 键 词：肾脏 缺血再灌注损伤 缺血后处理 BMP-7/Smad1/5/8信号通路 

分 类 号：R331.3[医药卫生—人体生理学] R965[医药卫生—基础医学]