| Objective: Postmenopausal osteoporosis(PMOP),I Osteoporosis, is the accelerated bone loss caused by an imbalance between Osteoclast bone absorption and formation of Osteoblast bone because of a deficiency of estrogen after the menopause. It is a kind of primary osteoporosis sickness. PMOP and the associated increased incidence of bone fractures is a major health problem in elderly women. Hormone replacement theropy, HRT, has been the priority to treat POMP. However, according to a new study, the risk-benefit ratio is not ideal by utilizing ERT as the first pripority.Therefore to effectively prevent and control PMOP becomes a question urgently to be solved in the medical arena. it is a current subject to discusses the PMOP pathogenesisin order to find a much safer and easyly-obtained medicine.The study, modeled on OVX (Ovariectomized Female Rat), using Aspirin as intervention factor, by examining the content of PGE2 in serum and the expression level of COX-2 on the bone tissues in each experimental group, explore the molecular mechanism of postmenopausal osteoporosis and develop specific medical intervention strategies to treat postmenopausal osteoporosis. The purpose of this study was to investigate the molecular mechanism of cyclooxygenase-2 inhibitor–Aspirin and whether it could be able to reduce bone loss.Methods:1 The grouping and duplication of model of postmenopausal osteoporosis50 female Sprague/Dawley rats at the age of 3 month were randomly divided into 5 groups(10 in each group):①Sham- operated(Sham);②OVX;③OVX treated with Nilesteriol(OVX+ E);④OVX treated with middle dose Aspirin (OVX+MAP);⑤OVX treated with lower dose Aspirin (OVX+LAP).Rats were given an intraperitoneal injection of 10% Chloral Hydrate (0.35ml/100mg weight) before surgery. Under aseptic condition, rats were open from the mid-line of back into the backside of the abdominal cavity, then remove ovaries for rats in group 2-group 4 and an equivalent weight of adipose tissue for rats in group 1.One week after surgery, rats in group 3 were treated with Nilesteriol at 1.0mg/kg per week, rats in group 4 were treated with Aspirin at 45 mg/kg per day, rats in group 5 were treated with Aspirin at 9 mg/kg per day, while rats in group 1 and group 2 were treated with an equivalent volume of saline per day. The dosages of drugs were proofread per week in accordance with their body weights.2 The establishment of postmenopausal osteoporosis model through dual-energy X-ray absorption method: 12 weeks after surgery, the bone density of the femurs were measured by the equipment of dual-energy X-ray bone density.3 Hematoxylin-eosin stain and immunohistochemistry stain, ELISA:The COX-2 levels in bone tissue were determined by immunohistochemistry techniques. After sacrificing the rats, we obtained the inferior extremity of femurs by sterile operation and performed hematoxylin-eosin stain and immunohistochemistry stain. ELISA detemination the content of PGE2 in serum.4 Result and image analysis:We applied One-Way ANOVA using Statistical Product and Service Solutons 17.0(SPSS17.0) for data analysis. All values were demonstrated by average±standard deviation(X-±S).And two-two comparison among the means were done by Student-Neuman-Keuls. P<0.05 was considered statistically significant.Results:1 The bone density:Compared with the sham-operated group, the BMD of the femur were reduced in OVX group and OVX+MAP and in OVX+LAP group(P<0.01;P<0.05;P<0.05);while there were no significant differences in OVX+E group(P>0.05);Compared with OVX group, the BMD of the femur were increased in OVX+E group and in OVX+M/LAP group(P<0.01,P<0.05).Compared with OVX+E group, there were no significant differences in OVX+APgroup(P>0.05).2 The characteristics of HE staining in bone tissues: (1) Sham operation group: bone trabecula plentiful,arranged densely,and the interval among trabeculae was narrow. (2) Ovariectomized group: the trabecular became thinner and irregular compared with sham group, the interval among trabeculae was broaden. (3) The OVX+E group share similar changes with sham-operated group, and the changes in OVX+MAP group and OVX+LAP group is between sham-operated group and the OVX group.3 The observation result of the immunohistochemistry stain the expression characteristic of COX-2 in bone tissue and marrow;The COX-2 positive signal is in the osteoblast around bone trabecula.There are obviously more positive cells around bone trabecula in Group OVX than in Group Sham, OVX+E, OVX+MAP and OVX+LAP, and its expression in OVX is more apparent than the other four groups.4 ELISA determination of the content of PGE2 in serum.Compared with the sham-operated group, the PGE2 in serum were increased in OVX group and in OVX+M/LAP group(P<0.01;P<0.05;P<0.05),while there were no significant differences in OVX+E group(P>0.05); Compared with OVX group, the PGE2 in serum were reduced in OVX+E group and in OVX+M/LAP group(P<0.01;P<0.05;P<0.05).Compared with OVX+E group, there were no significant differences in OVX+APgroup (P>0.05). Compared with OVX+MAP group, the PGE2 in serum were increased in OVX+LAPgroup (P<0.05).5 The correlation analysis result.The COX-2 levels are negatively correlated with the bone mineral density in OVX group and in OVX+AP group. There is no correlation between the expression of COX-2 with bone mineral density in Sham group and in OVX+E group. The content of PGE2 in serum are negatively correlated with the bone mineral density in OVX group and in OVX+M/LAP group. There is no correlation between the content of PGE2 in serum with bone mineral density in Sham group and in OVX+E group.Conclusions:1 Ovariectomized rats successfully established model of postmenopausal osteoporosis;2 Aspirin can significantly reduce the expression of COX-2 in OVX rats ,thereby preventing bone loss caused by OVX, the effect may be realization by inhibiting the expression of COX-2, COX-2 can be used as a cytokines to determining efficacy of prevention and treatment PMOP in clinical application.3 Aspirin led to a lower level of PGE2 in serum on OVX rats, PGE2 can be used as a immune factors to determine the efficacy of prevention and treatment PMOP in clinical application.4 Aspirin could be a useful therapeutic agent for the prevention of ovariectomy–induced bone loss;The mechanism of preventing bone loss by Aspirin is to inhibit the COX-2 enzyme by suppression of PGE2 activation in ovariectomized rats.
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