Angiotensin II-mediated improvement of renal mitochondrial function via the AMPK/PGC-1α/NRF-2 pathway is superior to norepinephrine in a rat model of septic shock associated with acute renal injury

Hui An; Zhenjie Hu; Yuhong Chen; Lianfang Cheng; Jian Shi; Linan Han

doi:10.21037/atm-21-621

Angiotensin II-mediated improvement of renal mitochondrial function via the AMPK/PGC-1α/NRF-2 pathway is superior to norepinephrine in a rat model of septic shock associated with acute renal injury

Ann Transl Med. 2021 Mar;9(6):481. doi: 10.21037/atm-21-621.

Authors

Hui An^{1

2}, Zhenjie Hu¹, Yuhong Chen¹, Lianfang Cheng², Jian Shi³, Linan Han¹

Affiliations

¹ Department of Intensive Care Unit, Hebei Medical University, Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, Shijiazhuang, China.
² Department of Intensive Care Unit, Baoding First Central Hospital, Baoding, China.
³ Cardiovascular Surgery Department, Baoding First Central Hospital, Baoding, China.

Abstract

Background: This study sought to compare the therapeutic effects of angiotensin II (ANG II) and norepinephrine (NE) on cecal ligation and puncture (CLP)-induced septic acute kidney injury (AKI) in rats.

Methods: Sepsis shock was induced in anesthesia Sprague-Dawley male rats by CLP model for 24 hours. A total of 40 rats were divided into five groups, including control group, sham group, CLP group, CLP + ANG II group, and CLP + NE group. CLP + ANG II and CLP + NE group were administration of ANG II or NE after sepsis shock respectively, maintaining the MAP at 75-85 mmHg. CLP group was administration of saline for contrast. At 0, 18, 24 hours measured the renal blood grades and resistant index (RI) by ultrasound equipment. At 6, 12, 18 and 24 hours collected 0.5 mL blood sample for creatinine and lactic acid examination. Rats were observed for 24 hours after CLP procedure and then sacrificed for subsequent examination, rat serum were used to determine the levels of inflammatory response factors, kidney tissues were used to examine the oxidative stress factors and mitochondrial related proteins." We added the sentence as following: "The AMPK, PGC-1α and NRF-2 expression in renal cortex was significantly increased in the CLP + ANG II group.

Results: Compared to the vehicle treatment, both ANG II and NE administration restored the decrease in the mean arterial pressure (MAP) and alleviated mitochondrial impairments in CLP rats. However, only ANG II alleviated CLP-induced abnormalities in serum creatinine and lactic acid concentrations, renal blood flow, the renal resistant index, renal histopathology, the production of proinflammatory cytokines, and oxidative stress markers in rats. ANG II was also found to be superior to NE in reversing the CLP-induced suppression of mitochondrial biogenesis-related protein expression in the kidneys of rats.

Conclusions: ANG II was better than NE in alleviating CLP-induced septic AKI in rats.

Keywords: Septic shock; acute kidney injury (AKI); angiotensin II; norepinephrine (NE); the AMPK/PGC-1α/NRF-2 pathway.