【摘要】 目的:研究HU-308药物缓释涂层对骨质疏松大鼠种植体周围骨组织内BMP-2、RANKL、OPG表达的影响。方法:60只大鼠随机分为去势手术组(M:M1、M2、M3)45只和假去势手术组(S)15只,通过去卵巢的方法建立绝经后大鼠骨质疏松模型。建模成功后,在大鼠双侧胫骨骭骺端按组别植入钛种植体,S、M1植入普通碱热处理种植体,M2植入肝素/壳聚糖涂层种植体,M3植入携带HU-308的肝素/壳聚糖涂层种植体。种植术后4、8、12周,采用免疫组织化学染色法观察种植体周围BMP-2、RANKL、OPG的表达情况,采用人工方法计算阳性细胞百分数对结果进行分析。结果:1.BMP-2阳性细胞百分数:术后4周,S>M2>M1组(P<0.05),M3>M2>M1组(P<0.05),M3略低于S组(P>0.05);术后8周,M3>M1>S组(P<0.05),M3>M2>S组(P<0.05),M2略大于M1组(P>0.05);术后12周,S显著小于M1、M2及M3组(P<0.05),M1、M2、M3组间差别无统计学意义;随着种植体植入时间增加,各组BMP-2阳性细胞百分数减小。2.R ANKL阳性细胞百分数:术后4、8周,M1>M2>S组(P<0.05),M1>M3>S组(P<0.05),M2略大于M3组(P>0.05);术后12周,S显著小于M1、M2及M3组(P<0.05),M1、M2、M3组间差别无统计学意义;随着种植体植入时间增加,各组RANKL阳性细胞百分数减小。3.OPG阳性细胞百分数:术后4、8周,S>M3>M1组(P<0.05),S>M3>M2组(P<0.05),M2略大于M1组(P>0.05);术后12周,S显著大于M1、M2及M3组(P<0.05),M1、M2及M3组间差别无统计学意义;随着种植体植入时间增加,各组OPG阳性细胞百分数减小。结论:随着植入时间增加,种植体周围骨组织内BMP-2、RANKL、OPG阳性表达降低;植入后同期比较,骨质疏松症大鼠种植体周围骨组织内OPG阳性表达低于健康大鼠,RANKL阳性表达高于健康大鼠;H U-308药物缓释涂层在种植体植入早中期使骨质疏松症大鼠种植体周围骨组织内BMP-2、OPG表达上升,R ANKL表达下降。更多还原

【Abstract】 Objective: To investigate the effects of sustained-release coatings of HU-308 on the expression level of BMP-2, RANKL, OPG in bone tissue around titanium implants in osteoporotic rats. Methods: Bilateral ovariectomy was performed in female rats to build model of steoporosis. The rats of Group S was sham operated and Group M(M1,M2, M3)was ovariectomized. After determining of the success of osteoporotic model, different titanium screws were implanted into the proximal metaphyses of all rats’ bilateral tibias. The rats of Group S and M1 were implanted with pure titanium screws of alkaline treatment. The rats of Group M2 were implanted with titanium screws of heparin/chitosan coated on. The rats of Group M3 were implanted with titanium screws of HU-308/heparin/chitosan coated on. The expression of the BMP-2, RANKL, OPG in bone tissue around the implants were detected by immunohistochemistry after 4, 8 and 12 weeks. The results were analyzed by calculating the percentage of the positive cells. Results: 1.The percentage of BMP-2 positive cells: 4 weeks after implantation, Group M3 and S were significantly higher than Group M2(P<0.05); Group M2 was higher than Group M1(P<0.05).8 weeks after implantation, Group M1 and M2 were significantly higher than Group S(P<0.05), lower than Group M3(P<0.05). 12 weeks after implantation, Group S was significantly lower than Group M1, M2 and M3(P<0.05). As time went on, the percentage of BMP-2 positive cells reduced.2.The percentage of RANKL positive cells: Group M2 and M3 were significantly higher than Group S but lower than Group M1(P<0.05)after 4 and 8 weeks.12 weeks after implantation,Group S was significantly lower than Group M1,M2 and M3(P<0.05). As time went on,the percentage of RANKL positive cells reduced.3.The percentage of OPG positive cells: 4 and 8 weeks after implantation, Group S was significantly higher than Group M3(P<0.05), Group M3 was significantly higher than Group M1 and M2(P<0.05). 12 weeks after implantation,Group S were significantly higher than Group M1,M2 and M3(P<0.05). As time went on,the percentage of OPG positive cells reduced. Conclusion:As time went on,BMP-2,RANKL and OPG expression in bone tissue around implants reduced. OPG expression in bone tissue around implants in osteoporotic rat was less than healthy rat and RANKL expression was more than healthy rat over the same perid. At the early-middle stage of implantation, HU-308/heparin-chitosan coated on titanium implants could increase the expression level of BMP-2,OPG and decrease the expression level of RANKL in bone tissue around implants in osteoporotic rats.更多还原