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To investigate the efficacy of the hypoxia-inducible factor-1α (HIF-1α) inhibitor PX-478 in improving radiation-induced apoptosis in cardiomyocytes and to elucidate its molecular mechanisms.
H9c2 cells were divided into blank group, model group, experimental-L group and experimental-H group. The experimental-L, -H groups were cultured with PX-478 at concentrations of 5 and 10 mol·L-1, respectively, while the other groups were cultured in normal medium. After 24 h of culture, all groups except the blank group were irradiated with 6 Gy X-rays to establish a model of radiation-induced cardiac injury and were subsequently cultured for another 24 h. Cell viability was assessed using the cell counting kit-8 assay; relative protein expression levels were determined by Western blotting; and apoptosis was detected using Annexin V/PI flow cytometry.
The relative expression levels of HIF-1α protein in the blank group, model group, experimental-L group and experimental-H group were 0.89±0.01, 1.05±0.01, 0.64±0.02 and 0.52±0.02; the relative expression levels of aquaporin-1 (AQP1) protein were 0.79±0.02, 0.94±0.02, 0.74±0.01 and 0.59±0.01; AQP4 protein levels were 0.89±0.01, 1.03±0.01, 0.68±0.01 and 0.50±0.01; B-cell lymphoma-2 (Bcl-2) protein levels were 0.78±0.02, 0.58±0.02, 1.00±0.03 and 0.82±0.03; Bcl-2-associated X protein (Bax) levels were 0.66±0.01, 0.96±0.01, 0.77±0.01 and 0.27±0.03; Caspase-3 levels were 0.83±0.01, 1.10±0.01, 0.71±0.02 and 0.30±0.01; the apoptosis rates were (4.05±0.60)%, (17.82±0.63)%, (9.35±0.41)% and (9.07±0.57)%, respectively. The above indicators in the blank, experimental-L, experimental-H groups showed statistically significant differences compared to the model group (all P<0.05).
PX-478 can improve radiation-induced cardiomyocyte edema and reduce apoptosis by inhibiting the abnormal activation of the HIF-1α/AQPs axis in H9c2 cells after irradiation, thereby regulating fluid metabolism.
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| 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 |
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