Abstract
Curcumin alleviates septic acute kidney injury (SAKI); however, the underlying mechanism remained unclear. To explore this, SAKI cell model and mice model were conducted by using LPS and cecal ligation and puncture (CLP), respectively. Cell counting kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA) assays indicated that LPS reduced the viability, but upregulated the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6, whereas Curcumin pretreatment had no effect on viability, but reduced the levels of TNF-α and IL-6. Further assays showed that Curcumin partly attenuated the LPS-induced injury as the viability was enhanced, TNF-α and IL-6 expressions and cell apoptosis rates were reduced. Western blot analysis indicated that Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3, p-65-NF-κB and cell apoptosis pathways were activated by LPS but suppressed by Curcumin. Mice SAKI model further indicated that the serum Cystatin C (Cys-C), creatinine (Cr) and blood urea nitrogen (BUN) were increased within 24 h of model construction while those indicators were decreased at 48 h. Pretreated with Curcumin, NF-κB inhibitor (PDTC) or JAK2 inhibitor (AG-490) could weaken the renal histological injury and the increased serum Cys-C, Cr and BUN, IL-6 and TNF-α induced by CLP. Moreover, PDTC, AG-490 and Curcumin all significantly reversed the previously increased expressions of p-JAK2/STAT3, p-p65 and proapoptotic proteins in the mice with AKI. The present study revealed that Curcumin attenuated SAKI through inhibiting NF-κB and JAK2/STAT3 signaling pathways, and proposed that Curcumin could be a potential therapeutic agent for treating SAKI.