The roles of AMPK/mTOR autophagy pathway in the acute kidney injury-induced acute lung injury

被引:2
|
作者
Shen, Si-Heng [1 ]
Wang, Ruo-Lin [1 ]
Yuan, Qi [1 ]
Jian, Lu-Yong [1 ]
Guo, Hua-Hui [1 ]
Li, He-Sheng [1 ]
Liu, Xue-Pin [1 ]
Huang, Ren-Fa [1 ,2 ]
机构
[1] Guangzhou Univ Chinese Med, Shenzhen Hosp Futian, Dept Nephropathy, Shenzhen, Peoples R China
[2] 6001 Beihuan Ave, Shenzhen, Peoples R China
来源
CHINESE JOURNAL OF PHYSIOLOGY | 2023年 / 66卷 / 02期
基金
中国国家自然科学基金;
关键词
Acute lung injury; AMPK; mTOR pathway; autophagy; inflammation; renal ischemic-reperfusion; ISCHEMIA-REPERFUSION INJURY; P62; LINKS; MTOR; AMPK; PATHOPHYSIOLOGY; INHIBITION; AKI;
D O I
10.4103/cjop.CJOP-D-22-00122
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Acute kidney injury (AKI) is one of the most challenging clinical problems in kidney disease due to serious complications and high mortality rate, which can lead to acute lung injury (ALI) through inflammatory reactions and oxidative stress. Adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway has been reported to be involved in the development of renal ischemia-reperfusion through autophagy and it remains unclear whether AMPK/mTOR pathway has an effect on the AKI-induced ALI. In this study, we aimed to investigate the effects of autophagy-related AMPK/mTOR signaling pathway on inflammatory factors and oxidative stress in an AKI-induced ALI model. The 48 male Sprague-Dawley rats were divided into four groups randomly: (i) sham, (ii) ischemia/reperfusion injury (IRI), (iii) IRI + rapamycin (RA), and (iv) IRI + 3-methyladenine (3-MA). Unilateral flank incisions were made and right kidneys were excised. The left kidney was subjected to 60 min of ischemia followed by 12, 24, 48, and 72 h of reperfusion. The levels of Scr, blood urea nitrogen (BUN), Wet/Dry ratio, indexes of inflammation, and oxidative stress were assayed. Histological examinations were performed. The protein expression of AMPK, mTOR, LC3-II/LC3-I ratio, and Beclin-1, ULK1 was evaluated by western blotting and immunohistochemistry. Compared to the rats from the sham group, IRI rats showed significantly pulmonary damage after AKI with increased Scr, BUN, Wet/Dry ratio, indexes of inflammation, and oxidative stress. The expression of AMPK, LC3-II/LC3-I ratio, Beclin-1, and ULK1 and were increased, while p62 and mTOR were decreased. In addition, RA treatment significantly attenuated lung injury by promoting autophagy through the activation of the AMPK/mTOR pathway, and 3-MA treatment exhibited adverse effects inversely. Therefore, the activation of the AMPK/mTOR pathway after renal IRI induction could significantly attenuate kidney injury and following AKI-induced ALI by inducing autophagy, which alienates inflammation, oxidative stress, and apoptosis.
引用
收藏
页码:73 / 84
页数:12
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