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目的研究雷洛昔芬(raloxifene,RLX)对兔骨折愈合的影响。方法健康新西兰大白兔80只,雌性44只,雄性36只,体重1.9～2.1kg。取72只动物制备左前肢桡骨中段0.5cm骨缺损模型,按给药不同分为4组,每组18只(雌性10只,雄性8只)。A、B、C组分别于术后第2天给予7.5、15.0、30.0mg(/kg·d)RLX至50d,D组不作处理。剩余8只不作任何处理,作为血清骨钙素检测正常对照。于术后不同时间点行骨密度、生物力学测定、X线片组织学和免疫组织化学染色观察,测定血清雌二醇、血浆胆固醇含量、血清骨钙素水平及子宫干重/体重比。结果术后20d各组骨密度达峰值,A、B、C组骨密度均高于D组(P<0.05);但A、B、C组间差异无统计学意义(P>0.05)。术后30、50d,A、B、C组最大破坏载荷和最大位移均较D组大(P<0.05);A、B、C组间差异无统计学意义(P>0.05)。术后7、20、30d,A、B、C组骨折X线评分较D组高(P<0.05);50d时B、C组与D组间及A、C组间比较差异均有统计学意义(P<0.05),B、C组间差异无统计学意义(P>0.05)。术后30、50d,A、B、C组骨折愈合处新骨面积百分比均高于D组(P<0.05)。术后30d,B、C组骨折愈合处ColⅡ蛋白分泌较D组增多(P<0.05),A、D组差异无统计学意义(P>0.05);50d时各组间差异均无统计学意义(P>0.05)。术后10、30及50d各组血清骨钙素水平均较正常对照动物明显增高(P<0.05);B、C组均较D组高(P<0.05);A组与D组比较,A、B、C组间比较差异均无统计学意义(P>0.05)。术后30d,各组血浆胆固醇含量无明显变化(P>0.05);50d时A、B、C组均明显降低,与D组比较差异有统计学意义(P<0.05)。术后30、50d,B、C组血清雌二醇含量与D组比较差异有统计学意义(P<0.05),余各组间比较差异无统计学意义(P>0.05)。术后30、50d,B、C组子宫干重/体重小于D组(P<0.05),A、D组差异无统计学意义(P>0.05)。结论以7.5mg(/kg·d)剂量口服RLX可安全有效促进兔桡骨缺损骨折模型骨折愈合。
Objective To investigate the effect of raloxifene (RLX) on fracture healing in rabbits. Methods Healthy New Zealand white rabbits 80, 44 females, 36 males, weighing 1.9 ~ 2.1kg. Totally 72 animals were used to prepare the 0.5cm bone defect model in the middle of the left forelimb. According to the different administration, they were divided into 4 groups (18 females and 8 males). Groups A, B and C received 7.5, 15.0 and 30.0 mg (/ kg · d) RLX on day 2 postoperatively, respectively, without treatment in group D. The remaining 8 without any treatment, as a serum osteocalcin test normal control. At different time points after operation, bone mineral density, biomechanical measurement, X-ray histology and immunohistochemical staining were performed to observe the serum estradiol, plasma cholesterol, serum osteocalcin and uterine dry weight / body weight ratio. Results The bone mineral density peaked at 20 days after operation in each group. The BMD in groups A, B and C were higher than that in group D (P <0.05). However, there was no significant difference between groups A, B and C (P> 0.05). At 30 and 50 days after operation, the maximum breaking load and maximum displacement of group A, B and C were higher than those of group D (P <0.05). There was no significant difference between group A, B and C (P> 0.05). At the 7th, 20th and 30th day after operation, the X-ray scores of fractures in groups A, B and C were higher than those in group D (P <0.05); at 50 days, the scores of B, C and D and A and C were statistically different (P <0.05), but no significant difference between B and C groups (P> 0.05). At 30 and 50 days after operation, the percentage of new bone area in fracture healing in groups A, B and C was higher than that in group D (P <0.05). At 30 days after operation, the secretion of ColⅡ protein in fracture healing group B and C increased more than that in D group (P <0.05), while there was no significant difference in group A and D (P> 0.05). There was no significant difference between the two groups (P> 0.05). The levels of serum osteocalcin in all groups at 10, 30 and 50 days after operation were significantly higher than those in normal control group (P <0.05), while those in groups B and C were significantly higher than those in D group (P <0.05) There was no significant difference between B and C groups (P> 0.05). At 30 days after operation, there was no significant change in plasma cholesterol (P> 0.05). On the 50th day, the levels of cholesterol in A, B and C groups were significantly lower than those in D group (P <0.05). The levels of serum estradiol in group B and group C at 30 and 50 days after operation were significantly different from those in group D (P <0.05). There was no significant difference among the other groups (P> 0.05). At 30 and 50 days after operation, the uterine dry weight / body weight in groups B and C was less than that in group D (P <0.05). There was no significant difference between groups A and D (P> 0.05). Conclusion The oral administration of RLX at a dose of 7.5 mg (/ kg · d) can effectively and effectively promote the fracture healing of rabbit radius-radial fracture models.