Lycium barbarum polysaccharides (LBP) suppresses hypoxia/reoxygenation (H/R)-induced rat H9C2 cardiomyocytes pyroptosis via Nrf2/HO-1 signaling pathway

This study aimed to explore the mechanism that Lycium barbarum polysaccharides (LBP) suppress hypoxia/reoxygenation (H/R)-caused pyroptosis in cardiomyocytes (H9C2) via the Nrf2/HO-1 pathway. Initially, we established the cell model of H/R (6 h hypoxia plus with 24 h reoxygenation), and found that 90 μg/mL LBP was the optimal concentration. Subsequently, we confirmed that LBP reduced the pyroptosis rate of cells after H/R, the activity of LDH, the inflammatory factors IL-1β and IL-18, and the levels of pyroptosis-specific markers ASC, NLRP3, and Caspase-1 (mRNAs and proteins). It increased the cell survival rate and the mRNA levels of the Nrf2/HO-1 pathway markers Nrf2 and HO-1, and allowed cytoplasmic Nrf2 protein to enter the nucleus to activate HO-1 protein. The Nrf2 siRNA2 caused the following events in H/R model: (1) the increases of the apoptosis rate, LDH activity, the levels of inflammatory factors (IL-1β and IL-18), the levels of ACS, NLRP3, and Caspase-1 (mRNAs and proteins); and (2) the decreases of the cell survival rate, the mRNA levels of Nrf2 and HO-1, and the protein levels of cytoplasm-Nrf2, nucleus-Nrf2, and HO-1. Therefore we concluded that 90 μg/mL LBP suppressed H/R-induced H9C2 cardiomyocyte pyroptosis via the Nrf2/HO-1 pathway.