Experimental Studies Of WH 60 On Prevention And Treatment Of Osteoporosis In Rats

Objective: To observe the effects of WH60 on osteoporosis in rats, and explore its possible mechanisms.Methods: 1.Experiment on inhibition effect of WH60 on rat osteoposis induced by dexamethasone: sixty female SD rats were chosen and were divided into six groups(control group, Dex model group,WH60 87.5,175 and 350 mg/kg groups, Vitamin D3 group).WH60 and Vitamin D3 were administered when the osteoporotic model was induced. Serum Ca²⁺, P³⁺, ALP, E₂, PTH, BGP were measured. The bone mineral density(BMD) and histomorphological features of femoral bone were also observed. 2.Experiment on therapeutic effect of WH60 on osteoposis in ovariectomized rats: sixty female SD rats were randomly assigned to six groups (n=10): sham operation group, osteoporotic model group, WH60 87.5 ,175,350 mg/kg groups,and nilestriol 1 mg/kg group. These experimental rats with the exception of sham operation group were ovariectomized and then administrated with WH60 or nilestriol for 12 weeks after 12 weeks of the ovariectomized operation. The rats were then killed and blood was taken for measurement of serum Ca²⁺, P³⁺, ALP, E₂, BGP, CT, TGF-β₁. BMD, body weight, uterus weight, pathomorphism of femur and uterus were observed as well.Results: 1.As compared with Dex model group, levels of serum Ca²⁺ and BGP in WH60 groups were increased(P<0.05 or P<0.01),respectively, while levels of serum P³⁺, ALP, E2 and PTH in WH60 groups were deceased(P<0.05 or P<0.01), respectively. WH60 could markedly improve the morphological construction and BMD of femoral bone in rats. 2.At 24 weeks after ovariectomy, serum Ca²⁺, E₂, CT, TGF-β₁ levels and BMD in osteoporotic model group were decreased(P<0.05 or P<0.01), but serum level of P³⁺ was increased in some degree, serum ALP and BGP levels were significantly increased(P<0.05 or P<0.01), femur trabecular bone was narrow, medullary cavity was bigger, endometrial epithelial cells were atrophied. After treatment with WH60 for 12 weeks, serum Ca²⁺, E₂, CT, TGF-β₁ levels and BMD were increased(P<0.05 or P<0.01), while the serum ALP and BGP were kept in high levels, the trabecular bone was more widened and less broken, medullary cavity became smaller. Differences in body weight, the weight and pathomorphism of uterus were not found as compared with osteoporotic model group.Conclusion: 1.WH60 could prevent the osteoporotic generation induced by Dex in female rats, its mechanisms might be associated with restoring the imbalance of E₂ and PTH induced by Dex and stimulating bone formation by increasing the level of BGP. 2. WH60 had therapeutic effect on osteoporosis in ovariectomized rats, its mechanisms might be associated with stimulating bone formation by increasing the levels of serum E₂, BGP and TGF-β₁ , and restraining bone resorption by increasing the levels of serum CT. 3.WH60 could increase the serum E₂ level, but there were little effects on uterus weight and histomorphology, it suggested that WH60 might include the active constituents of selective estrogen receptor modulators.