The Effect and Mechanism of Shuling-jiangu Prescription on Bone Mineral Density in Osteoporosis Animal Models
Objective To explore the effect and mechanism of Xulingjiangu formula on bone mineral density in osteoporosis rats.Methods Fifty female SD rats were divided into sham operation group,model group and Xulingjiangu prescription intervention group(low,medium and high dose)according to random number table method,with 10 rats in each group.The osteoporosis model was established by bilateral oophorectomy in both the model group and the intervention group.After 30 days of modeling,the administration was started by intragastric administration,in which the low,medium and high dose groups were given 7.5 mg/kg,15 mg/kg and 30 mg/kg Xulingjiangu prescription by intragastric administration,respectively,and the sham operation group and model group were given equal volume 0.9%sodium chloride injection.After 12 weeks of continuous administration,bone mineral density,bone microstructure and bone biomechanics were detected.Serum levels of bone protective protein and tartrate-resistant acid phosphatase were detected by enzyme-linked immunosorbent assay(ELISA).mRNA expression levels in p38 mitogen-activated protein kinase signaling pathway were detected by Real-time PCR.Results The maximum bone load,three-point bending stress and bone mineral density of rats in the 5 groups had significant differences,among which the sham operation group was significantly higher than the other 4 groups,and the model group was significantly lower than the other 4 groups.With the increase of administration dose,the maximum load,three-point bending stress and bone mineral density of rats in the intervention group showed a significant increase trend,and the difference was statistically significant(P＜0.05).After 12 weeks of treatment,the number of bone trabeculae,the thickness of bone trabeculae and the ratio of bone surface area to volume in the intervention group were significantly higher than those in the model group,and with the increase of dose,all values showed a significant increasing trend(P＜0.05).The bone trabecular space in the intervention group was significantly lower than that in the model group,and the trend was significantly decreased with the increase of dose,the difference was statistically significant(P＜0.05).After treatment for 12 years,the level of anti-tartrate acid phosphatase in the model group was significantly increased,and higher than that in the sham operation group,while the level of anti-tartrate acid phosphatase in the intervention group was significantly decreased,and with the increase of dose,the level of anti-tartrate acid phosphatase was significantly decreased,the difference was statistically significant(P＜0.05).The level of serum osteophosphtin in the model group was significantly decreased,while the level of serum osteophosphtin in the intervention group was significantly increased,and with the increase of dose,the level of serum osteophosphtin was significantly increased,with statistical significance(P＜0.05).The mRNA expression levels of serum MKK4,P38α,P38γ,matrix metalloproteinase-3 and matrix metalloproteinase-13 in the model group were significantly higher than those in the sham operation group and the intervention group.The mRNA expression levels of serum MKK4,P38α,P38γ,matrix metalloproteinase-3 and matrix metalloproteinase-13 were significantly decreased,and the difference was statistically significant(P＜0.05).Conclusion By inhibiting p38 mitogen-activated protein kinase signaling pathway,Hueling Jiangu prescription can improve bone microstructure and increase bone density,thus effectively preventing and treating osteoporosis.
p38 mitogen-activated protein kinaseOsteoporosisBone mineral densityBone microstructureBone biomechanics
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