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年轻的系统性环境可减轻老年小鼠的肾缺血再灌注损伤。

Youthful systemic milieu alleviates renal ischemia-reperfusion injury in elderly mice.

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, Air Force General Hospital, Chinese PLA, Beijing, China.

Department of Nephrology, Air Force General Hospital, Chinese PLA, Beijing, China.

出版信息

Kidney Int. 2018 Aug;94(2):268-279. doi: 10.1016/j.kint.2018.03.019. Epub 2018 Jun 21.

DOI:10.1016/j.kint.2018.03.019
PMID:29935950
Abstract

The incidence of acute kidney injury (AKI) is high in elderly people, and is difficult to prevent and treat. One of its major causes is renal ischemia-reperfusion injury (IRI). A young systemic environment may prevent the senescence of old organs. However, it is unknown whether a young milieu may reduce renal IRI in the elderly. To examine this question, bilateral renal IRI was induced in old (24 months) mice three weeks after parabiosis model establishment. At 24 hours after IRI, compared to old wild-type mice, the old mice with IRI had significantly damaged renal histology, decreased renal function, increased oxidative stress, inflammation, and apoptosis. However, there was no increase in autophagy. Compared to old mice with IRI, old-old parabiosis mice with IRI did not show differences in renal histological damage, oxidative stress, inflammation, apoptosis, or autophagy, but did exhibit improved renal function. Compared to the old-old parabiosis mice with IRI, the old mice with IRI in the young (12 week)-old parabiosis showed less renal histological injury and better renal function. Renal oxidative stress, inflammation, and apoptosis were significantly decreased, and autophagy was significantly increased. Thus, a youthful systemic milieu may decrease oxidative stress, inflammation, and apoptosis, and increase autophagy in old mice with IRI. These effects ameliorated IRI injuries in old mice. Our study provides new ideas for effectively preventing and treating AKI in the elderly.

摘要

急性肾损伤(AKI)在老年人中的发病率很高,且难以预防和治疗。其主要原因之一是肾脏缺血再灌注损伤(IRI)。年轻的全身环境可能会阻止老年器官的衰老。然而,年轻的环境是否可以减轻老年人的肾脏 IRI 尚不清楚。为了研究这个问题,我们在建立联体模型 3 周后,对老年(24 个月)小鼠进行双侧肾脏 IRI。在 IRI 后 24 小时,与老年野生型小鼠相比,IRI 后的老年小鼠肾脏组织学损伤明显,肾功能下降,氧化应激、炎症和细胞凋亡增加。然而,自噬没有增加。与IRI 后的老年小鼠相比,IRI 后的老年-老年联体小鼠在肾脏组织学损伤、氧化应激、炎症、细胞凋亡或自噬方面没有差异,但肾功能得到改善。与IRI 后的老年-老年联体小鼠相比,IRI 后的年轻(12 周龄)联体小鼠的肾脏组织学损伤较小,肾功能较好。肾脏氧化应激、炎症和细胞凋亡显著减少,自噬显著增加。因此,年轻的全身环境可能会减少氧化应激、炎症和细胞凋亡,并增加 IRI 后老年小鼠的自噬。这些作用改善了老年小鼠的 IRI 损伤。我们的研究为有效预防和治疗老年人 AKI 提供了新的思路。

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