AIM To study the mechanism of polydatin(PD)in inhibiting myocardial cell pyroptosis induced by high glucose based on silence information regulator1(Sirt1)-forkhead transcription factor O1(FoxO1)signal pathway.METHODS Cardiac cell H9c2 was taken as the research object and the PD concentration was screened by different concentrations of PD treatment.Cells were grouped into model group,PD low,medium and high dose groups(PD-L,M,H,20,40,80 μmol/L),blank control group(control)and Sirt1 inhibitor group[PD-H+sirtinol(10 μmol/L)].Cell Counting Kit-8(CCK8)method was applied to detect the cell activity and enzyme-linked immunosorbent assay(Elisa)method was used to measure the release of lactate dehydrogenase(LDH)and the level of Interleukin-1β(IL-1β).The level of reactive oxygen species(ROS)was detected by Dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescence probe,the charred cells were detected by flow cytometry and the expression levels of Nod-like receptor protein 3(NLRP3)mRNA and gasdermin D(GSDMD)mRNA in cells were detected by real-time fluorescence quantitative PCR.Western blot was applied to detect the protein expression.RESULTS Compared with those in control group,the cell activity in model group decreased(P＜0.01)and after treatment with different concentrations of PD,the cell activity increased gradually(P＜0.01).Compared with those in control group,LDH release,IL-1β level,ROS level,pyroptosis rate,NLRP3 mRNA,GSDMD mRNA expressions,and expressions of pyroptosis protein NLRP3,c-caspase-1,GSDMD and GSDMD-N in model group increased,and the expression of Sirt1-FoxO1 signal pathway protein decreased(P＜0.01).Compared with those in model group,LDH release,IL-1β level,ROS level,scorching rate,NLRP3 mRNA,GSDMD mRNA expressions,and expressions of scorching protein NLRP3,c-caspase-1,GSDMD and GSDMD-N in PD group and sirtinol group decreased,and the expression of Sirt1-FoxO1 signal pathway protein increased(P＜0.05).Sirtinol reversed the protective effect of PD on myocardial cell pyroptosis induced by high glucose.CONCLUSION PD can improve the inflammatory injury of cells and inhibit the high glucose-induced myocardial cell pyroptosis by up-regulating the expression of Sirt1-FoxO1 signal pathway protein.
关键词
虎杖苷/心肌细胞焦亡/炎症/Sirt1-FoxO1信号通路
Key words
polydatin/myocardial cell pyroptosis/inflammation/Sirt1-FoxO1 signal pathway
维普
万方数据