To explore the underlying mechanism of TanshinoneⅡA (TanⅡA) exerted in myocardial infarction (MI) through nuclear factor E2-related factor 2 (NRF2)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/pyroptosis axis.
SD rats were randomly divided into sham operation group [only exposed the heart without left anterior descending (LAD) ligation], model group (LAD ligation) and experimental group (LAD ligation and 10 mg·kg-1 TanⅡA). 2,3,5-Triphenyte-trazoliumchloride (TTC) staining was used to detect the area of infarction; Western blot was utilized to investigate the expression level of NRF2, NLRP3 and gasdermin D (GSDMD) in myocardial tissue. The H9c2 cells were divided into blank group (normal culture), model group [oxygen-glucose deprivation (OGD) culture], control group (normal culture and 40 μmol·L-1 TanⅡA) and combined group (OGD culture and 40 μmol·L-1 TanⅡA). Western blot was utilized to investigate the expression level of NRF2, GSDMD in cardiomyocyte. Creatine kinase MB (CK-MB) in cell culture supernatant were detected by automatic biochemical analyzer.
The proportion of myocardial infarction area in the sham operation group, model group and experimental group were 0, (58.64±13.41)% and (41.69±8.73)%, respectively; the relative expression of NLRP3 protein were 1.01±0.10, 2.12±0.26 and 1.48±0.11, respectively; the relative expression of GSDMD protein were 1.03±0.17, 2.22±0.20 and 1.40±0.17, respectively; the relative expression of NRF2 protein were 1.12±0.29, 0.51±0.02 and 0.96±0.10, respectively; the indicators of the model group compared with the sham operation group, and the indicators of the experimental group were compared with the model group, the differences were statistically significant (all P<0.05). The CK-MB in blank group, model group, control group and combined group were (54.30±19.24), (208.60±38.19), (46.76±13.63) and (126.10±42.87) U·L-1, respectively; the relative expression of NRF2 protein were 1.37±0.14, 0.44±0.08, 1.34±0.17 and 0.79±0.11, respectively; the relative expression of GSDMD protein were 0.95±0.26, 1.97±0.17, 1.04±0.20 and 1.16±0.16, respectively. The indicators of the model group compared with the blank group, and the indicators of the combined group were compared with the model group, the differences were statistically significant (all P<0.05).
TanⅡA can alleviate myocardial infarction-induced myocardial injury through regulation NRF2/NLRP3/pyroptosis axis.
| 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 |