P53-P21-Rb信号通路在缺血再灌注损伤后期肾小管上皮细胞衰老中的作用

Effect of P53-P21-Rb Pathway on Tubular Cell Senescence in the Later Phase after Renal Ischemia/Reperfusion Injury

目的研究P53-P21-Rb信号通路在肾脏缺血再灌注损伤(ischemia/reperfusion injury,IRI)后期肾小管上皮细胞衰老中的作用。方法建立P53(+/+)和P53(-/-)鼠单侧肾脏IRI模型,研究IRI后期不同时间点肾小管上皮细胞的衰老变化以及P52、P21和Rb蛋白表达的变化。结果P53鼠肾脏在IRI后期,肾小管上皮细胞衰老在IRI后3个月和6个月点显著增加(P<0.05);而P53(+/+)鼠对侧肾和P53(-/-)鼠双肾,在IRI后1个月和3个月点几乎没有出现肾小管上皮细胞衰老;P53(-/-)鼠的IRI肾在IRI后6个月点也只检测到少量衰老的肾小管上皮细胞,细胞衰老与P53、P21和Rb蛋白的表达有相关性(P<0.05)。结论P53-P21-Rb信号通路的激活在IRI诱导肾小管上皮细胞衰老的发生中可能发挥着重要作用。

Objective To investigate the course of tubular cell senescence and expression of P53, P21 and Rb during the late phase of ischemia/reperfusion injury （IRI） in kidney, and assess the effects of P53 - P21 - Rb pathway on tubular cell senescence. Methods Experimental models of unilateral renal IRI were used in P53 （ ＋ / ＋ ） and P53 （ - / - ） mice ; progress of cell senescence and expression of Rb, P21 and/or P53 proteins in tubular cells were studied at different time points after IRI. Results For kidneys of P53 （ ＋ / ＋ ） mice in later phase of IRI, senescent tubular cells were significantly increased at 3 and 6 months after IRI. In contrast, in contralateral kidneys from P53 （ ＋ / ＋ ） and in both kidneys from P53 （ - / - ） mice, almost no senescent cells were observed at 1 and 3 month after IRI ; a few senescent cells were detected in IRI kidneys of P53 （ - / - ） mice at 6 month. Changes of cell senescence were correlated with the expression level of P53, P21 and Rb proteins in mice of either genotype. Conclusion The activation of P53 - P21 - Rb signaling pathway may play a vital role in tubular cell senescence induced by IRI.