Luteolin alleviates sepsis-induced cardiac injury by activating SIRT1

Abstract

Objective To explore the effect and mechanism of luteolin (LTN) in sepsis-induced cardiac injury. Methods Caecal ligation perforation (CLP) was used to establish a septic model in mice, and 42 mice were randomly divided into Sham group, CLP group and CLP+LTN group, with 14 mice in each group. The 48-hour survival rate was observed. Ultrasonography was used to detect cardiac function, Western blotting was employed to detect the expression of SIRT1, p-p65 and p65, and PCR was applied to measure the mRNA levels of inflammatory cytokines. In in vitro study, LPS of 1 μg/mL was used to treat mouse macrophagocyte RAW 264.7, and then the medium was used to treat mouse cardiomyocytes HL-1. LPS-treated RAW 264.7 cells and RAW 264.7+LPS medium-treated HL-1 cells were co-cultured with different concentrations of LTN, and the optimal LTN concentration was determined by TNF-α ELISA kit and CCK-8 assay. Then after SIRT1 expression of RAW 264.7 cells and HL-1 cells was knocked down by siRNA, the expression of above proteins was detected by Western blotting, and mRNA expression levels of inflammatory cytokines were measured by PCR, ATP content was detected by reagent kit, and cell viability was detected by CCK-8 assay. Results The mice of the CLP group had significantly lower 48-hour survival rate, cardiac function and SIRT1 expression (P < 0.05), and increased protein level of p-p65/p65 and mRNA levels of IL-1, TNF-α and IL-6 (P < 0.05) when compared with the Sham group. However, these effects were reversed by LTN treatment (P < 0.05). In RAW 264.7 cells, LTN treatment significantly reversed LPS-induced decrease of SIRT1 expression, and increases in protein level of p-p65 and mRNA levels of IL-1, TNF-α and IL-6 (P < 0.05). Nevertheless, SIRT1 knockdown abolished the effect of LTN (P < 0.05). In HL-1 cells, LTN treatment significantly reversed the decrease of SIRT1 expression, ATP content and cell viability induced by RAW 264.7+LPS medium (P < 0.05), but this effect could be partially eliminated by SIRT1 knockdown (P < 0.05). Conclusion LTN can inhibit inflammatory response and enhance the anti-inflammatory effect of cardiomyocytes by activating SIRT1, and thus reduce sepsis-induced cardiac dysfunction.

Keywords

• luteolin
• sepsis
• sirt1
• cardiac dysfunction
• inflammatory response