To explore the effects and mechanism of zoledronic acid on bone metabolism in osteoporosis rats under hypoxic environment.
The rat model of osteoporosis in hypoxia environment was established by bilateral ovary extraction combined with low-pressure oxygen chamber feeding, and was randomly divided into model group, control group and experimental -L, -M, -H groups, with 10 rats per group; another 10 normal rats were selected as the normal group. Experimental -L, -M, -H groups were given 2.5, 5.0 and 10.0 mg·kg-1 zoledronic acid by subcutaneous injection, once a week. Control group was given 0.105 mg·kg-1 estradiol valerate by intragastric administration, once a day. Normal and model groups were injected with equivalent 0.9% NaCl by subcutaneous injection. Six groups were treated for 4 weeks. The serum levels of tartrate-resistant acid phosphatase (TRAP), alkaline phosphatase (ALP) and bone gla protein (BGP) were detected by enzyme-related immunosorbent assay. The bone mineral density (BMD) was measured by dual-energy X-ray. The expression levels of mitogen extracellular signal-regulated kinase (MEK)/extracellular regulated protein kinases (ERK) in femur were detected by Western blot.
The TRAP levels of experimental-M, experimental -H, control, model and normal groups were (78.06±1.16), (69.39±1.44), (70.19±1.24), (94.39±1.04) and (64.95±1.19) U·L-1; the ALP levels were (61.72±3.10), (45.40±0.82), (43.53±1.52), (88.69±2.29) and (42.01±1.56) U·L-1; the BGP levels were (14.82±0.28), (12.29±0.28), (12.92±0.29), (19.96±0.46) and (11.79±0.59) ng·mL-1; the BMD levels were (0.28±0.02), (0.35±0.04), (0.38±0.03), (0.16±0.02) and (0.41±0.06) g·cm-2; the relative expression levels of p-MEK protein were 0.64±0.06, 0.84±0.05, 0.78±0.01, 0.15±0.06 and 0.88±0.04; the relative expression levels of p-ERK protein were 0.70±0.03, 0.95±0.02, 0.84±0.07, 0.29±0.03 and 0.97±0.06, respectively. Compared with the model group, the above indexes in the experimental-M, -H groups and control group were statistically significant (all P<0.05).
Zoledronic acid can improve bone mineral density and bone metabolism in hypoxic osteoporosis rats, the mechanism may be related to the regulation of MEK/ERK pathway.
| 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 |