To explore the mechanism of tacrolimus mediating the protective effect on chronic glomerulonephritis (CGN) rats through regulating the expression of microRNA-145-5p (miR-145-5p) and modulating the C-X-C motif chemokine ligand 16/Ras homolog family member A/Rho-associated coiled-coil-containing protein kinase (CXCL16/RhoA/ROCK) pathway.
SD rats were randomly divided into the control group (administered an equal volume of 0.9% NaCl), model group (CGN model + equal volume of 0.9% NaCl), experimental group (CGN model + 3 mg·kg-1·d-1 tacrolimus) and combined group (experimental group + tail vein injection of 140 nmol·L-1 miR-145-5p antagomir). Enzyme-linked immunosorbent assay was used to measure 24-hour urinary protein (PRO), blood urea nitrogen (BUN), and serum creatinine (SCr) levels. Real-time quantitative polymerase chain reaction was used to detect the relative expression level of miR-145-5p in rat kidney tissue; Western blotting was used to determine protein expression levels.
The 24-hour PRO levels in the control, model and experimental groups were (7.44±2.16), (85.29±17.35) and (49.81±9.52) mg, respectively; the BUN levels were (5.82±1.03), (9.65±1.78) and (6.97±1.14) mmol·L-1, respectively; the SCr levels were (46.31±7.69), (93.57±16.94) and (58.72±8.36) μmol·L-1, respectively. The relative expression levels of miR-145-5p in the control, model, experimental and combined groups were 1.00±0.14, 0.56±0.07, 0.83±0.12 and 0.68±0.09, respectively; the TNF-α levels were (116.42±14.53), (237.56±26.18), (164.79±18.35) and (205.12±21.64) pg·mL-1, respectively; the IL-1β levels were (15.76±1.84), (52.41±6.27), (21.35±2.92) and (43.63±4.58) pg·mL-1, respectively; the IL-6 levels were (26.28±3.47), (71.53±8.64), (38.92±5.06) and (59.78±6.21) pg·mL-1, respectively; the CXCL16 expression levels were 1.00±0.12, 1.62±0.17, 1.23±0.14 and 1.45±0.15, respectively. Statistical analysis revealed significant differences between the model group and the control group, between the experimental group and the model group, and between the combined group and the experimental group for these indicators (P<0.05, P<0.01, P<0.001).
Tacrolimus can upregulate miR-145-5p, activate the CXCL16/RhoA/ROCK pathway, reduce inflammatory factors, and improve kidney damage in CGN rats.
| 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 |