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To investigate the mechanism of action of bezafibrate (BEZ) targeting nuclear factor of activated T cells 5 (NFAT5) through microribonucleic acid (miR)-486-5p on the kidney tissues of mice with diabetic nephropathy.
Db/m mice were used as control group. Db/db mice were used to construct a diabetic nephropathy model, which was divided into 4 groups according to the random number table method: Model group, experimental group (75 mg·kg-1·d-1 BEZ), miR-486-5p antagomir group (75 mg·kg-1·d-1 BEZ+10 mg·kg-1 miR-486-5p antagomir), sh-NFAT5 group (75 mg·kg-1·d-1 BEZ+10 mg·kg-1 miR-486-5p antagomir+recombinant adenovirus containing NFAT5 knockdown plasmid). The kit was used to detect the levels of renal function and oxidative stress in mice; and the expression levels of glucose metabolism and renal fibrosis-related proteins in renal tissues of mice in each group were detected by Western blot.
The levels of malondialdehyde (MDA) in the control group, model group, experimental group, miR-486-5p antagomir group, and sh-NFAT5 group were (2.78±0.56), (4.96±0.97), (3.02±0.54), (4.51±0.79) and (3.24±0.58) nmol·mg-1, respectively; the levels of aldose reductase (AR) were 1.00±0.12, 3.61±0.43, 1.82±0.29, 3.09±0.58 and 2.25±0.47, respectively; the levels of pyruvate dehydrogenase (PDH) were 1.00±0.11, 0.53±0.10, 0.91±0.15, 0.64±0.12 and 0.82±0.14, respectively; the levels of pyruvate dehydrogenase E1 subunit α1 (PDHA1) were 1.00±0.14, 0.36±0.07, 0.83±0.16, 0.51±0.11 and 0.74±0.13, respectively; the levels of pyruvate dehydrogenase kinase (PDK) were 1.00±0.10, 2.59±0.52, 1.34±0.31, 2.11±0.43 and 1.56±0.39, respectively; the levels of transforming growth factor-β1 (TGF-β1) were 1.00±0.11, 3.15±0.52, 1.43±0.38, 2.72±0.43 and 1.89±0.57, respectively; the levels of fibronectin (FN) were 1.00±0.09, 2.84±0.57, 1.46±0.41, 2.59±0.52 and 1.73±0.49, respectively; the levels of collagen type I (Collagen I) were 1.00±0.13, 4.28±0.71, 2.03±0.46, 3.64±0.68 and 2.51±0.53, respectively. The above indicators of the control group were compared with the model group, the above indicators of the model group were compared with the experimental group, the above indicators of the experimental group were compared with the miR-486-5p antagomir group, and the above indicators of the miR-486-5p antagomir group were compared with the sh-NFAT5 group. The differences were statistically significant (P<0.05, P<0.01, P<0.001).
BEZ can effectively protect the kidney tissue of mice with diabetic nephropathy, and the mechanism may be realized through the miR-486-5p/NFAT5 signaling pathway.
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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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