Abstract
Objective To investigate the effects of pitavastatin on lipopolysaccharide(LPS)-induced H9c2 cells and its mechanism.Methods H9c2 cells were divided into control group,model group(treated with 10 μg·mL-1 LPS),experimental group(after 1 μmol·L-1 pitavastatin treatment,10 μg·mL-1 LPS treatment),and combination group[treated with 1.28 μmol·L-1 NLR family pyrin domain containing protein 3(NLRP3)agonist on the basis of experimental group].The NLRP3/cysteine-requiring aspartate protease 1(caspase-1)/gasdermin D(GSDMD)signaling pathway related protein levels were detected by Western blot.The messenger ribonucleic acid(mRNA)relative expression levels related to inflammation and mitochondrial function were detected by quantitative real time polymerase chain reaction.Results The relative expression levels of NLRP3 protein in control group,model group,experimental group and combination group were 1.00±0.15,2.56±0.38,1.35±0.19 and 2.15±0.31,respectively;the relative expression levels of caspase-1 protein were 1.00±0.18,1.88±0.22,1.22±0.20 and 1.75±0.22,respectively;the relative expression levels of GSDMD protein were 1.00±0.14,2.12±0.32,1.55±0.21 and 1.99±0.23,respectively;the relative expression levels of tumor necrosis factor-α mRNA were 1.00±0.15,4.12±0.65,2.11±0.29 and 3.54±0.48,respectively;the relative expression levels of interleukin-1β mRNA were 1.00±0.18,3.33±0.39,1.42±0.25 and 2.23±0.33,respectively;the relative expression levels of interleukin-18 mRNA were 1.00±0.14,2.28±0.28,1.33±0.26 and 1.98±0.22,respectively;the relative expression levels of PPAR-γ coactivator 1 alpha(PGC-1α)mRNA were 1.00±0.14,0.45±0.07,0.89±0.12 and 0.61±0.08,respectively;the relative expression levels of mitochondrial transcription factor A mRNA were 1.00±0.19,0.53±0.07,0.77±0.09 and 0.58±0.08,respectively;the relative expression levels of nuclear respiratory factor-1 mRNA were 1.00±0.17,0.62±0.08,0.85±0.13 and 0.65±0.08,respectively;the relative expression levels of uncoupling protein 2 mRNA were 1.00±0.15,0.34±0.05,0.92±0.16 and 0.48±0.07,respectively.The above indexes in model group were compared with those in control group,those in experimental group were compared with those in model group,and those in combination group were compared with those in experimental group,the differences were statistically significant(all P＜0.05).Conclusion Pitavastatin can inhibit inflammation,reduce pyroptosis of H9c2 cells,and protect mitochondrial function,which may be achieved by inhibiting the NLRP3/caspase-1/GSDMD signaling pathway.关键词
匹伐他汀/线粒体/细胞焦亡/心肌细胞/NLR家族Pyrin域蛋白3/半胱氨酸蛋白酶-1/成孔蛋白信号通路Key words
pitavastatin/mitochondria/pyroptosis/cardiomyocyte/NLR family pyrin domain containing protein 3/cysteine-requiring aspartate protease 1/gasdermin D signaling pathway分类
医药卫生
