Role of SIRT1/Nrf2 signaling pathway in berberine-induced reduction of renal ischemia-reperfusion injury in mice / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of silencing information regulator 1 (SIRT1)/nuclear factors E2-related factor2 (Nrf2) signaling pathway in berberine-induced reduction of renal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 5 groups ( n=6 each) using a random number table method: sham operation group (S group), renal I/R group (RIR group), berberine+ I/R group (B group), berberine+ I/R+ SIRT1 inhibitor EX527 group (BE group) and berberine+ I/R+ Nrf2 inhibitor ATRA group (BA group). After the right kidney was removed, the left renal artery was clamped for 45 min followed by reperfusion to establish the model of renal I/R injury.In B, BE, and BA groups, berberine 100 mg·kg -1·d -1 was given for intragastric administration at 14 days before surgery.In group BE and group BA, EX527 5 mg·kg -1·d -1 and ATRA 10 mg·kg -1·d -1 were injected intraperitoneally at 3 days before surgery, respectively.The equal volume of normal saline was given for 14 consecutive days in group S and group RIR.Blood samples were collected from orbital vein at 24 h of reperfusion for measurement of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations, for determination of the interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) contents (by enzyme-linked immunosorbent assay) and expression of SIRT1, Nrf2, apoptosis-associated speck-like protein containing CARD (ASC), caspase-1, nucleotide-binding oligomerization domain-like receptor containing pyrin domain (NLRP3) (by Western blot) and for examination of the pathological changes of renal tubules (with a light microscope). The damage to the renal tubules was scored. Results:Compared with group S, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly increased in RIR, B, BE and BA groups, the expression of SIRT1, Nrf2, ASC, caspase-1 and NLRP3 was up-regulated in RIR, BE and BA groups, and the expression of SIRT1, Nrf2, caspase-1 and NLRP3 was up-regulated in group B ( P<0.05). Compared with group RIR, the concentrations of serum Cr and BUN, the contents of renal IL-1β and TNF-α and renal tubular injury score were significantly decreased in B, BE and BA groups, the expression of SIRT1 and Nrf2 in group B, Nrf2 and ASC in BE group and SIRT1, ASC and caspase-1 in BA group was up-regulated, and the expression of ASC, caspase-1 and NLRP3 in group B, SIRT1 and NLRP3 in BE group and Nrf2 in BA group was down-regulated ( P<0.05). Compared with group B, the serum concentrations of Cr and BUN, the contents of IL-1β and TNF-α and renal tubular injury score were significantly increased in BE and BA groups, the expression of ASC, caspase-1 and NLRP3 in BE and BA groups was up-regulated, and the expression of SIRT1 in BE and Nrf2 in BA groups was down-regulated ( P<0.05). Conclusion:SIRT1/Nrf2 signaling pathway is involved in the process of berberine-induced reduction of renal I/R, which is related to inhibiting pyroptosis in mice.