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To explore the effect of the Mst1/Nrf2 pathway on myocardial autophagy function in type 2 diabetic mice, and to verify whether Mst1 gene knockout and Nrf2 activation can improve diabetic cardiomyopathy (DCM) by regulating autophagy.
The experimental animals were randomly divided into the following 4 groups, with 8 animals in each group: Control group (6 C57BL/6N mice, standard diet), DCM group (6 C57BL/6N mice), DCM+Mst1-/- group (6 Mst1 gene knockout mice), high-sugar and high-fat diet, DCM+Mst1-/-+Nrf2 group (6 diabetic mice with Mst1 gene knockout intervened by Tert-butylhydroquinone(tBHQ)(50 mg/kg/day)(PHR3512, Sigma-Aldrich). Cardiac function was detected by blood pressure, and autophagy was analyzed by Western blot.
The 4w systolic blood pressures of the control group, the high glucose control group, the high glucose Mst1 knockout group, and the high glucose Mst1-/-±Nrf2 group were (103.6±1.43), (117.23±9.80), (111±7.43) and (109.21±3.22) mmHg, respectively, and the 8w systolic blood pressures were (99.09±1.46), (135.78±5.98), (123.57±8.90) and (119.97±6.97) mmHg, respectively. the 12w systolic blood pressures were (106.67±2.32), (138.90±2.00), (126.68±2.98) and (120.63±3.12) mmHg, respectively. The diastolic blood pressures at 4w were (79.50±1.12), (99.24±3.89), (85.03±1.89) and (82.90±3.22) mmHg, respectively. The diastolic blood pressures at 8w were (76.35±2.12), (106.78±5.98), (94.80±3.90) and (88.90±2.90) mmHg, respectively. The diastolic blood pressure at 12w were (78.79±1.70), (101.32±2.13), (93.62±3.98) and (89.02±1.92) mmHg, respectively. The 4-week mean arterial pressures were (87.51±0.41), (117.23±9.80), (85.56±1.46) and (83.91±2.23) mmHg, respectively. The 8-week mean arterial pressures were (84.24±2.41), (116.46±5.68), (104.80±3.91) and (98.90±2.90) mmHg, respectively. the 12-week mean arterial pressures were (86.09±1.74), (101.32±2.13), (103.60±3.37) and (99.02±1.55) mmHg, respectively. Compared with the mice in the Control group, the systolic blood pressure, diastolic blood pressure and mean arterial pressure of the mice in the DCM group, DCM+Mst1-/- group and DCM+Mst1-/-+Nrf2 group were significantly increased (P<0.000 01).
Improved cardiac diastolic function in mice with Mst1/Nrf2 activation. This effect is achieved by reducing the expression of p62 protein, further emphasizing that the Mst1/Nrf2 axis exerts its protective function by regulating autophagy-related proteins.
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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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