Lycium barbarum polysaccharides (LBP) suppresses hypoxia/reoxygenation (H/R)-induced rat H9C2 cardiomyocytes pyroptosis via Nrf2/HO-1 signaling pathway
Yi Qin Gao, Huangen Li, Yongkang Que, Wei‐Wen Chen, Shiying Huang, Wenjie Liu, Xiaotong Ye
Abstract
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 apoptosis 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. • LBP protected H9C2 against H/R-injury, and reduced the levels of pyroptosis-specific markers ASC, NLRP3 and Caspase-1. • LBP allowed cytoplasmic Nrf2 protein to enter the nucleus to activate HO-1 protein. • Nrf2 siRNA2 blocked the protection of LBP inH9C2 cells after H/R. • LBP could suppresses H/R-induced H9C2 cardiomyocytes pyroptosis via Nrf2/HO-1 signaling pathway.