Effect of NLRP3 in liver tissues of mice with hepatic ischemia-reperfusion injury

Abstract

Objective According investigate the expression of NLRP3 in liver tissues of mice with hepatic ischemia-reperfusion injury (HIRI), to determin the role of NLRP3 in the process of HIRI. Methods Established mice model of partial HIRI. Forty-two male C57BL/6 mice (aged 7 to 8 weeks, weight 20 to 25 g) were respectively divided into 7 groups: no-treatment control group, sham operation group, HIRI groups (2、6、12、24 h) and CY-09 group, 6 mice in each group. The injury of the hepatic tissues in the 7 groups was analyzed based on detecting the levels of alanine transaminase (ALT), aspartate transaminase (AST), interleukin-1β (IL-1β), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α) by ELISA. HE and TUNEL staining were used to observe the pathological changes of liver tissues after HIRI. Western blotting assay were carried out to detect the expressions of NLRP3 and Caspase-1. Measurement data were expressed as mean±standard deviation (Mean±SD), and one-way variance analysis was used for comparison between groups. If the variance was not uniform, Dunnett C test was used. Results Serum ALT, AST, IL-1β, IL-18 and TNF-α of mice detected in HIRI groups were higher than no-treatment control group and sham operation group at all endpoints (P<0.05). The relative expression of NLRP3 and Caspase-1 in the liver tissues of mice in the HIRI groups were significantly higher than that in the no-treatment control group and sham operation group. Serum ALT, AST, IL-1β, IL-18 and TNF-α of mice detected in CY-09 group were lower than HIRI groups at all endpoints (P<0.05). Less hepatocellular necrosis were exhibited in CY-09 group, comparing to HIRI groups. The hepatocyte apoptosis rate of mice in the CY-09 group was significantly lower than that in the 12 h HIRI group (P<0.05). The relative expression of NLRP3 in the liver tissues of mice in the CY-09 group was significantly lower than that in other groups. The relative expression of Caspase-1 in the liver tissues of mice in the CY-09 group was significantly lower than that in other groups except the no-treatment control group and sham operation group. Conclusions HIRI cause an increase in NLRP3 expression. The inhibition of NLRP3 can reduce HIRI. Key words: Liver diseases; Reperfusion injury; Ischemia; Mice; NLRP3