目的:研究去卵巢及辛伐他汀(simvastatin,SVS)对大鼠骨痂骨保护素(osteoprotegerin,OPG)表达的影响。方法:2月龄雌性SD大鼠采用去卵巢(ovariectomy,OVX)方法模拟人绝经后骨质疏松症,造模成功后进一步建立胫骨骨折髓内钉内固定模型。大鼠分为3组:假手术组(sham+vehicle)、空白组(OVX+vehicle)及实验组(OVX+SVS)。OVX+SVS组于骨折端皮下注射辛伐他汀(10 mg.kg-1.d-1×5 d),sham+vehicle及OVX+ve-hicle组仅注射无辛伐他汀的空白溶剂。骨折后1、2、4周取骨痂标本,切片免疫组化染色,分析骨痂中的增殖细胞核抗原(PCNA)、OPG表达情况。结果:结果显示OVX+vehicle组骨折后1、2、4周PCNA阳性率较sham+vehicle组分别下降17.3%、32.1%和26.1%(P〈0.01);OVX+SVS组骨折后1、2、4周PCNA阳性率较OVX+vehicle组分别增加60.1%、67.7%和67.7%(P〈0.01);半定量结果显示OVX+vehicle组OPG表达水平最低,sham+vehicle组最高,而OVX+SVS组的OPG表达水平介于2组之间,OVX+SVS组与OVX+vehicle组间差异显著(P〈0.01)。结论:本实验显示去势可明显减少骨痂OPG的表达,而辛伐他汀可刺激骨痂分泌OPG,提示他汀类药物具有间接抑制破骨细胞的作用。
AIM: To investigate the effect of ovariectomy(OVX) and simvastatin(SVS) on the expression of osteoprotegerin(OPG) in bone callus of rats.METHODS: Simvastatin(10 mg·kg-1·d-1) was injected subcutaneously to tissue overlying the site of fractured tibiae of ovariectomized rats for a treatment period of 5 days.Vehicle reagent was used as control in sham and OVX rats.Bone callus were harvested at time points of 1,2 and 4 weeks after fracture and the expression of proliferating cell nuclear antigen(PCNA) and OPG was measured by the method of immunohistochemistry.RESULTS: Compared with OVX+vehicle group,the expression of PCNA decreased by 17.3%,32.1% and 26.1% in OVX+vehicle group than that in sham+vehicle group(P0.01),and increased by 60.1%,67.7% and 67.7% in OVX+SVS group(P0.01) at the time points of 1,2 and 4 weeks after fracture,respectively.The expression of OPG was the lowest in OVX+vehicle group.The significant differences of OPG expression between OVX+SVS group and OVX+vehicle group at the 3 time points(P0.01),and significant differences of OPG expression between sham+vehicle group and OVX+vehicle group at 1st week and 2nd week after fracture(P0.05) were observed.CONCLUSION: Ovariectomy decreases the expression of OPG in bone callus of rats,while simvastatin increases it,indicating that simvastatin can indirectly inhibit the function of osteoclasts.