Curcumin inhibits NLRP3 inflammasome reduction on the early myocardial damage in septic rats / 中华急诊医学杂志

ABSTRACT

Objective:To investigate the effect of curcumin on the nucleotide-binding oligomerization domain-like receptor protein (NLRP3) inflammasome in cardiomyocytes of rats with early sepsis and its mechanism.Methods:Twenty-four male SD rats were randomly divided into three groups the sham-operated group (sham group, n=8), the sepsis group ( n=8), and the curcumin intervention group (Cur group, n=8). A rat model of sepsis was prepared by cecal ligation and perforation (CLP). After modeling, 100 mg/kg of curcumin was intraperitoneally injected and repeated 24 h later. Rats in the sepsis group were injected with normal saline. The levels of myocardial injury-specific troponin T (cTnT) in rat plasma were detected by ELISA at 6, 24, and 48 h. Hematoxylin-eosin (HE) staining was used to observe the pathological injury of the myocardium in the myocardial tissue of rat at 48 h. The apoptosis of cardiomyocytes was detected by TUNEL assay. The expression levels of Cleaved caspase-1, NLRP3 and IL-1β protein were detected by Western blot, and the ultrastructural changes of the cardiomyocytes were observed under a transmission electron microscope. Results:The levels of cTnT in rat plasma at 6, 24, and 48 h in the Cur group were significantly lower than those in the sepsis group ( P<0.05). HE staining showed infiltration, cell edema and necrosis of myocardial inflammatory cells in the sepsis group, while only partial cell edema and necrosis were observed in the Cur group. TUNEL assay showed that the apoptosis of cardiomyocytes in the Cur group was significantly lower than that in the sepsis group [(28.4±2.3)% vs. (43.6±3.8)%, P<0.05]. The expression levels of Cleaved caspase-1, NLRP3 and IL-1β in the Cur group were lower than those in the sepsis group and higher than those in the sham-operated group ( P<0.05). Under transmission electron microscopy, the nuclei in the sham-operated group had intact membranes and uniform chromatin distribution; in the sepsis group chromatin margination, pyknosis, mitochondrial cristae breakage, cavitation, and partial breakage of sarcomere were observed; while in the Cur group partial chromatin margination, slightly edema and dilation of mitochondria, with basically complete morphology were observed. Conclusions:Curcumin inhibits NLRP3-mediated acute myocardial injury in septic rats, and its mechanism may be related to pyroptosis induced by the down-regulation of the expression of Cleaved caspase-1 and IL-1β protein.