ISSN 1006-298X      CN 32-1425/R

Chinese Journal of Nephrology, Dialysis & Transplantation ›› 2022, Vol. 31 ›› Issue (6): 537-543.DOI: 10.3969/j.issn.1006-298X.2022.06.007

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Irisin plays a protective role in sepsis associated acute kidney injury by upregulating the expression of mitochondrial UCP2

  

  • Online:2022-12-28 Published:2023-01-04

Abstract: Objective:To investigate whether irisin has a protective effect on sepsis associated acute kidney injury (SAAKI) with sepsis and its mechanism.
Methodology:In vivo and in vitro animal models were established using LPS. Serum creatinine and blood urea nitrogen were measured by automatic biochemical analyzer. Hematoxylin eosin staining was used to observe renal pathological changes. Apoptosis was detected by TUNEL assay. The expressions of UCP2, Bcl2, ccaspase3, Bax, IL1β, IL6, TNFα, KIM1, AMPK, pAMPK and GAPDH were detected by Western blotting. The levels of IL1β, IL6 and TNFα were detected by ELISA. The mRNA levels of UCP2, FNCD5 and AMPK were detected by RTqPCR.
Results:In vivo: Intraperitoneal injection of LPS resulted in renal dysfunction and increased renal tubule injury score in mice. Irisin supplementation could significantly improve renal function and reduce the injury score. Studies showed that irisin significantly reduced the levels of inflammatory factors (TNFα, IL1β and IL6) and improved the inflammatory response of SAAKI. The levels of Bcl2, ccaspase3 and Bax and TUNEL assay showed that irisin significantly improved cell apoptosis. In vitro: ROS levels in HK2 cells were determined, indicating that irisin significantly improved the oxidative stress response of SAAKI. By studying the linear relationship between irisin and AMPK and UCP2, we found that irisin may play a role by upregulating UCP2 expression in SAAKI through AMPK/UCP2 signal transduction pathway.
Conclusion:Irisin plays a protective role in SAAKI by upregulating the expression of mitochondrial UCP2. Irisin may be a potential therapeutic agent for LPSinduced AKI.

Key words: sepsis, acute kidney injury, irisinuncoupling protein 2, AMP-activated protein kinase