动物造模 z-bio 2021-09-04 715

　　Objective To analyze the effects of simvastatin and risedronate sodium alone and in combination on dexamethasone-induced osteoporosis in rats.

　　Method This study used female 3-month-old SD rats, divided into five groups (8 in each group): control group, osteoporosis model group, simvastatin group, risedronate sodium group and combination medication group. Except for the control group, rats in the other groups were injected subcutaneously with dexamethasone (2.5 mg, twice a week), and the drug intervention group was given simvastatin 5 mg/kg, risedronate sodium 0.1 mg/kg and both The combined intervention was performed once a day, and all rats were sacrificed after 8 weeks to obtain materials. After taking the left femur to detect its bone density, the three-point bending experiment was used to analyze its maximum load, and the left tibia was taken to detect the bone mass and microstructure parameters of the proximal cancellous bone by micro-computed tomography (micro-CT). The right femur was embedded in decalcified paraffin, and immunohistochemical staining was used to detect the expression of OPG and RANKL, and RNA from the right tibia was extracted to detect the expression of osteoprotegerin (OPG) and osteoclast differentiation factor (RANKL).

　　Results (1) Bone mineral density: The model group (0.207±0.02) g/cm² was significantly lower than the other groups, the simvastatin group (0.226±0.023) g/cm², the risedronate sodium group (0.237±0.021) g/ cm² was significantly lower than the control group (0.282±0.013) g/cm² combined medication group (0.257±0.012) g/cm² (P<0.05). (2) Biomechanics: Maximum load: The model group (90.2±7.1) was significantly lower than the control group and the combination group (P<0.05). (3) micro-CT: The number of trabecular bone (Tb.N) and trabecular bone volume fraction (BV/TV) in the model group were significantly lower than the other 4 groups, and the trabecular bone separation (Tb.Sp) was significantly higher than the others 4 groups (P<0.05), simvastatin group (21.6±2.8), risedronate sodium group (21.9±2.6) BV/TV was significantly lower than the control group (29.5±2.7), the combination group (25.3±2.9) ), TbSp was significantly higher than the control group (P<0.05). (4) Immunohistochemical staining: OPG: model group, risedronate sodium group and combination medication group were significantly lower than the control group (P<0.05), group C and E were significantly higher than the model group (P<0.05) . The expression of RANKL in the model group, simvastatin group, risedronate sodium group, and combination group was significantly higher than that of the control group (P<0.05), and the expression of RANKL in the E group was significantly lower than that of the model group (P<0.05). (5) PCR: The expression of OPG in the model group (0.74±0.17) was significantly lower than that of the control group (1.00±0.16) and the simvastatin group (1.27±0.19) (P<0.05); the expression of RNAKL in the model group was significantly higher than that of the others Group (P<0.05), the simva│statin group (1.31±0.16) was significantly higher than the control group (1.00±0.18).

　　Conclusion Dexamethasone can induce the establishment of a rat model of bone loss, and the combined treatment of simvastatin and risedronate sodium can partially prevent the bone loss and bone quality decline of this model, and the effect is better than that of single medication.