Acute kidney injury (AKI) is a common clinical disease. Ferropotosis, a new type of regulatory cell death, serves an important regulatory role in AKI. Pachymic acid (PA), a lanostane-type triterpenoid from Poria cocos, has been reported to be protective against AKI. However, the protective mechanism of PA in AKI is not yet fully understood. The present study aimed to investigate the effect and molecular mechanism of PA on ferroptosis in renal ischemia reperfusion injury in vivo. A total of 30 mice were intraperitoneally injected with 5, 10 and 20 mg/kg PA for 3 days. A bilateral renal pedicle clip was used for 40 min to induce renal ischemia-reperfusion injury and establish the model. The results demonstrated that treatment with PA decreased serum creatinine and blood urea nitrogen, and ameliorated renal pathological damage. Transmission electron microscopy revealed no characteristic changes in ferroptosis in the mitochondria of the renal tissue in the high-dose PA group, and only mild edema. Furthermore, treatment with PA increased glutathione expression, and decreased the expression levels of malondialdehyde and cyclooxygenase 2. Treatment with PA enhanced the protein and mRNA expression levels of the ferroptosis related proteins, glutathione peroxidase 4 (GPX4), solute carrier family 7 (cationic amino acid transporter, y+ system) member 11 (SLC7A11) and heme oxygenase 1 (HO-1) in the kidney, and increased the expression levels of nuclear factor erythroid derived 2 like 2 (NRF2) signaling pathway members. Taken together, the results of the present study suggest that PA has a protective effect on ischemia-reperfusion induced acute kidney injury in mice, which may be associated with the inhibition of ferroptosis in the kidneys through direct or indirect activation of NRF2, and upregulation of the expression of the downstream ferroptosis related proteins, GPX4, SLC7A11 and HO-1.

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Background: It is well demonstrated that intraoperative blood pressure is associated with postoperative acute kidney injury (AKI); however, the association between severity and duration of abnormal intraoperative blood pressure (BP) with AKI in patients undergoing laparoscopic surgery remains unknown. Methods: This retrospective cohort study included 12,414 patients aged ≥ 18 years who underwent a single elective laparoscopic abdominal surgery during hospitalization between October 2011 and April 2017. Multivariate stepwise logistic regressions were applied to determine the correlation between the severity and duration of intraoperative mean arterial pressure (MAP, (systolic BP + 2 × diastolic BP)/3), acute intraoperative hypertension (IOTH) and postoperative AKI, in different periods of surgery. Results: A total of 482 hospitalized patients (3.9%) developed surgery-related AKI. Compared with those without IOTH or with preoperative mean MAP (80–85 mmHg), acute elevated IOTH (odds ratio, OR, 1.4, 95% CI, 1.1 to 1.7), mean MAP 95–100 mmHg (OR, 1.8; 95% CI, 1.3 to 2.7), MAP 100–105 mmHg (OR, 2.4; 95% CI, 1.6 to 3.8), and more than 105 mmHg (OR, 1.9; 95% CI, 1.1 to 3.3) were independent of other risk factors in a diverse cohort undergoing laparoscopic surgery. In addition, the risk of postoperative AKI appeared to result from long exposure (≥20 min) to IOTH (OR, 1.9; 95% CI, 1.5 to 2.5) and MAP ≥ 115 mmHg (OR, 2.2; 95% CI, 1.6 to 3.0). Intraoperative hypotension was not found to be associated with AKI in laparoscopic surgery patients. Conclusions: Postoperative AKI correlates positively with intraoperative hypertension in patients undergoing laparoscopic surgery. These findings provide an intraoperative evaluation criterion to predict the occurrence of postoperative AKI.