OBJECTIVE To investigate the effect of stachydrine (STA) on hypoxia inducible factor-1α (HIF-1α)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathway in hypoxia/reoxygenation (H/R) induced cardiomyocyte pyroptosis model. METHODS H9C2 cardiomyocytes were separated into control group (Control group), model group (H/R group), H/R+low concentration STA group (H/R+STA-L group, 5 μmol·L-1), H/R+medium concentration STA group (H/R+STA-M group, 10 μmol·L-1), H/R+high concentration STA group (H/R+STA-H group, 20 μmol·L-1), H/R+high concentration STA (20 μmol·L-1)+HIF-1α activator group [H/R+STA-H+dimethyloxaloglycine(DMOG) group, 20 μmol·L-1 STA+10 μmol·L-1 DMOG]. H9C2 cell viability was tested by cell counting kit-8(CCK-8) assay. H9C2 cell apoptosis was measured by flow cytometry. The levels of IL-1β, IL-18, and LDH in cells were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of IL-1β, IL-18, Caspase-1, HIF-1α, and NLRP3 were quantified using Western blot. RESULTS Compared with the control group, the cell survival rate of the H/R group decreased (P<0.05), the positive expression rate of Caspase-1, levels of IL-1β, IL-18, LDH, and protein expression of Caspase-1, IL-1β, IL-18, HIF-1α, and NLRP3 increased (P<0.05). Compared with the H/R group, the cell survival rates of the H/R+STA-L group, H/R+STA-M group and H/R+STA-H group increased, the positive expression rate of Caspase-1, levels of IL-1β, IL-18, LDH, and protein expression of Caspase-1, IL-1β, IL-18, HIF-1α, and NLRP3 reduced (P<0.05). Compared with the H/R+STA-H group, the cell survival rate of the H/R+STA-H+DMOG group obviously reduced (P<0.05), the positive expression rate of Caspase-1, levels of IL-1β, IL-18, LDH, and protein expression of Caspase-1, IL-1β, IL-18, HIF-1α, and NLRP3 obviously increased (P<0.05). CONCLUSION STA can inhibit H/R induced cardiomyocyte pyroptosis, and its mechanism may be related to the HIF-1α/NLRP3 signaling pathway.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |