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年轻血液环境可降低老年小鼠肾脏衰老程度。

A Young Blood Environment Decreases Aging of Senile Mice Kidneys.

机构信息

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Department of Nephrology, Zhongshan Hospital, Fudan University, Kidney and Dialysis Institute of Shanghai, Kidney and Blood Purification Laboratory of Shanghai, China.

出版信息

J Gerontol A Biol Sci Med Sci. 2018 Mar 14;73(4):421-428. doi: 10.1093/gerona/glx183.

Abstract

Whether changes in internal body environment affect kidney aging remains unclear. Specifically, it is unknown whether transplanted kidneys from older donors recover from tissue damage after placement in younger recipients. In this study, a parabiosis animal model was established to investigate the effects of a young internal body environment on aged kidneys. The animals were divided into six groups: young (Ycon) and old control (Ocon) groups, isochronic youth-youth group (Y-IP), elderly-elderly group (O-IP), and heterochronic youth (Y-HP) and elderly (O-HP) groups. After parabiosis, tubule and interstitial tissue scores in the O-HP group were significantly lower than in the Ocon and O-IP groups. The expression of aging-related protein p16 and SA-β-gal in the O-HP group was significantly reduced compared with the Ocon and O-IP groups. Autophagy factors Atg5 and LC3BII were significantly upregulated, whereas the expression of the autophagic degradation marker (P62) was significantly downregulated in the O-HP group compared with the Ocon and O-IP groups. With the same comparison, the positive cells of TUNEL staining and the expression of IL-6 and IL-1β were significantly reduced, whereas the total/cleaved caspase-3 and total/pNF-κB were significantly increased in the O-HP group. The results demonstrated that a young blood environment significantly reduces kidney aging. These findings provide new evidence supporting an increase in the upper age limit for human kidney transplantation donors.

摘要

内体环境变化是否影响肾脏衰老尚不清楚。具体而言,尚不清楚来自老年供体的移植肾脏在年轻受者体内是否能从组织损伤中恢复。在这项研究中,建立了联体动物模型来研究年轻内体环境对老年肾脏的影响。动物被分为六组:年轻(Ycon)和老年对照组(Ocon)、同年龄青年联体(Y-IP)、老年联体(O-IP)以及异龄青年联体(Y-HP)和老年联体(O-HP)。联体后,O-HP 组的肾小管和间质组织评分明显低于 Ocon 和 O-IP 组。O-HP 组衰老相关蛋白 p16 和 SA-β-gal 的表达明显低于 Ocon 和 O-IP 组。自噬因子 Atg5 和 LC3BII 明显上调,而自噬降解标志物(P62)的表达在 O-HP 组明显低于 Ocon 和 O-IP 组。同样的比较显示,O-HP 组的 TUNEL 染色阳性细胞和 IL-6 和 IL-1β 的表达明显减少,而总/裂解 caspase-3 和总/pNF-κB 的表达明显增加。结果表明,年轻的血液环境显著降低了肾脏衰老。这些发现为增加人类肾脏移植供体的最高年龄限制提供了新的证据。

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