曲古抑菌素A促进去卵巢大鼠钛植入物骨整合

Trichostatin A enhances titanium implant osseointegration in ovariectomized rats

目的探讨TSA对去卵巢大鼠TI骨整合的影响。方法将30只健康3月龄雌性SD大鼠随机分为Sham组(n=5)和OVX组(n=25)。正常饲养3个月后,两组各选取5只大鼠处死,取股骨远端样本行Micro-CT和HE染色以鉴定是否成功建立骨质疏松模型。随后在OVX组剩余大鼠双侧股骨干骺端植入直径1.5 mm TI,并将其分为2组:Control组(n=10)和TSA组(n=10)。连续给药4周。给药结束后处死全部大鼠并取股骨样本行Micro-CT扫描、HE染色以及Masson染色,ELISA法检测,拔钉实验。结果与Sham组对比,Micro-CT显示OVX组BMD、BV/TV、Tb.Th、Tb.N降低(P<0.05),而Tb.Sp、SMI升高(P<0.05),HE染色显示OVX组骨小梁数量明显降低。与Control组对比,Micro-CT显示TSA组BMD、BV/TV、Tb.Th、Tb.N、Conn.D均升高(P<0.05),而Tb.Sp、SMI降低(P<0.05),HE染色、Masson染色显示TSA组骨小梁数量、新生骨数量均升高,ELISA法检测结果显示TSA组OCN、BMP2均升高,拔钉实验显示TSA组TI轴向拔出力增大。结论TSA通过上调OCN、BMP2等成骨相关蛋白,促进骨小梁形成和新骨形成,进而改善去卵巢大鼠TI骨整合。

Objective To investigate the effect of trichostatin A(TSA)on titanium implant(TI)osseointegration in ovariectomized rats.Methods 3-Month-old female Sprague-Dawley rats(n=30)were randomly divided into Sham group(n=5)and OVX group(n=25).After 3 months of normal feeding,5 rats in each group were randomly selected and were sacrificed.The distal femurs were harvested for evaluation with high-resolution micro-CT.HE staining was used to verify the establishment of osteoporosis model.TI was inserted bilaterally in the femoral metaphyseal region of remaining rats in OVX group.All the TI implanted rats were randomly divided into 2 groups:Control group(n=10)and TSA group(n=10).The rats in TSA group were intraperitoneally injected trichostatin A for 4 weeks.The rats in Control group were intraperitoneally injected the same amount of normal saline.All the rats were sacrificed after the drug treatment and the distal femurs were harvested for evaluation with highresolution micro-CT,HE staining,and Masson staining.The serum of the rats was examined using ELISA.Results Compared with those in Sham group,micro-CT result showed that bone mineral density(BMD),bone volume fraction(BV/TV),trabecular thickness(Tb.Th),trabecular number(Tb.N),and connective density(Conn.D)in OVX group decreased(P<0.05),and trabecular separation(Tb.Sp)and structure model index(SMI)increased(P<0.05)in OVX group.HE staining result showed that Tb.N in OVX group significantly decreased.Compared with those in the Control group,BMD,BV/TV,Tb.Th,and Tb.N increased in TSA group(P<0.05),and Tb.Sp and SMI decreased(P<0.05).HE staining and Masson staining result showed that Tb.N and new bone increased in TSA group.ELISA result showed that bone morphogenesis-related proteins bone morphogenetic protein-2(BMP2)and serum osteocalcin(OCN)increased in TSA group.Conclusion TSA improves TI implant osseointegration by promoting bone trabecular formation in OVX rats by up-regulating the key proteins of bone formation OCN and BMP2.