辛伐他汀不同干预方案对骨质疏松大鼠骨质量的影响

目的探讨和比较不同干预方案下辛伐他汀对去卵巢大鼠骨丢失和骨质量下降的干预效果。方法3月龄雌性SD大鼠32只,随机分为4组,每组8只:假手术(A)组、卵巢切除(B)组、卵巢切除加辛伐他汀前半程干预组(C)和后半程干预组(D)。除A组接受假手术外,其余各组大鼠行双侧卵巢切除术,C组于术后给予辛伐他汀(5 mg/kg/d)干预10周后停药,D组于术后10周开始接受辛伐他汀干预。术后20周处死所有大鼠,采用酶联免疫吸附测定法(ELISA)检测血清I型前胶原氨基端前肽(PINP)、I型胶原羧基端交联端肽(ICTP)水平,取第3、4、5腰椎,双能X线法检测大鼠第3腰椎骨密度,压缩试验检测第4腰椎侧最大载荷、弹性模量等生物力学指标,微计算机断层扫描技术(micro-CT)检测第5腰椎松质骨骨量和微观结构。结果 (1)血清学检测结果:B、C、D组PINP和ICTP均显著高于A组;(2)骨密度:B组显著低于其余各组,C、D组显著低于A组(P0.05);(3)生物力学:最大载荷、弹性模量B组显著低于其余3组(P0.05)、C、D组显著低于A组(P0.05);4、micro-CT:A组骨容积率(BV/TV)、骨小梁数量(Tb.N)显著高于其余3组,骨小梁分离度(Tb.Sp)显著低于其余3组(P0.05),C、D组Tb.Sp显著低于B组(P0.05)。结论大鼠去卵巢20周后发生明显骨量丢失和骨质量下降,选择前半程干预和后半程干预均能部分阻止该模型骨量丢失、微结构退变和力学性能下降,但骨密度均不能恢复到正常水平。

Effects of simvastatin treatment with different intervention programs on the bone quality of osteoporotic rats

Objective To investigate the effects of simvastatin on the bone loss and deterioration of bone quality with different intervention programs. Methods Thirty two 3-month-old female Sprague-Dawley (SD) rats were randomized into 4 groups of 8 animals in each: All rats but those in the sham group (A) received bilateral ovariectomy, and treated by vehicle (B), simvastatin (5 mg/kg/day) at first half period (C) or at latter half period (D). The rats in group C received simvastatin by a gavage after the OVX operation immediately, and stopped at 10 weeks after OVX. The rats in group D began to receive simvastatin treatment from 10 weeks after OVX and ended at 20 weeks after OVX. At week 20, all rats were sacrificed and the concentrations of serum PINP and ICTP were detected by ELISA, L3 vertabra was used to detect the bone mineral density, L4 vertebra was used to analyze the maximum loading and elastic modulus by compression test, and the microstructure of the L5 vertebra was detected by micro-computed tomography. Results 1. ELISA analysis: the concentrations of serum P1NP and ICTP in the groups A, B and C were significantly higher than that of group A (P<0.05). 2. BMD test showed that the rats in group B had significantly lower BMD than the other 3 groups (P<0.05), while the BMD of groups C and D were markedly lower than that of group A (P<0.05). 3. Biomechanical test: the maximum load and elastic modulus of L4 vertebrae in the group B were significantly lower than the other 3 groups (P<0.05), and those of the groups C and D were markedly lower than that in the group A (P<0.05). 4. micro-CT: BV/TV and Tb.N in the sham operated rats were significantly higher than those of the other 3 groups, while the opposite trends was found in Tb.Sp (P<0.05), and the Tb.Sp in the groups C and D were significantly lower than that of group B (P<0.05). Conclusions Our data demonstrate that bone loss and deterioration of bone micro-structure and biomechanical properties occurred at 20 weeks after ovariectomy, both the first-half-period and latter-half-period treatment by simvastatin may partially prevent these changes, but can not restore the BMD to normal level.