雄激素与辛伐他汀对去势大鼠骨质疏松的治疗作用及其机制

Therapeutic effectsand mechanismsof androgen and simvastatin on osteoporosis incastrated rats

目的 探讨辛伐他汀及雄激素对去睾丸的SD雄鼠骨质疏松治疗作用,并初步探讨其作用机制.方法 将50只12个月龄SD雄性大鼠数字随机分为去势组（A）、假手术组（B）、雄激素组（C）、辛伐他汀组（D）、雄激素＋辛伐他汀组（E）,每组10只.除假手术组外所有大鼠行睾丸及附睾切除术.术后第9周开始药物干预,各组给予相应药物灌胃12周,去势组和假手术组给予相同剂量生理盐水灌胃.于手术前、给药前、给药后6周、12周测各组大鼠腰椎骨密度,并于给药12周后处死大鼠后分别进行白细胞介素6（IL-6）、骨钙素（BGP）、血钙等的测定,并观察骨组织学表现.结果 药物干预12周后骨密度C组（0.250 ±0.176） g/cm2、D组（0.237±0.023） g/cm2与A组（0.188±0.019）g/cm2比较差异有统计学意义（P＜0.01）,而E组在药物干预6周后（0.260±0.017）g/cm2与A组（0.208±0.022） g/cm2、C组（0.246±0.122） g/cm2、D组（0.237±0.025） g/cm2比较差异即有统计学意义（P＜0.05）;A组BGP（0.908±0.069） ng/ml显著低于B组（1.658±0.191） ng/ml,E组（1.898 ±0.238） ng/ml显著高于B组,差异均有统计学意义（均P＜0.05）,而C组、D组与B组骨钙素比较无统计学差异;各药物组的血清IL-6,与B组比较无显著性差异,与A组比较明显降低（P＜0.05）,而C组、D组、E3组之间比较无明显差异.结论 辛伐他汀与雄激素联合应用,可协同抑制骨吸收促进骨形成,从而可明显改善骨质疏松.

Objective To study the therapeuticeffects and mechanismsof androgen and simvastatin on osteoporosis in castrated rats.Methods Fifty 12-month-old male SD rats were divided into five groups randomly：castrated group （A）,sham operated group （B）,androgen group （C）,simvastatin group （D）,androgen ＋ simvastatin group（E）.Each group has 10 rats.In this study,osteoporosis model was established by castration.All the groups were given testis and epididymis resection except sham operatedgroup.The drugs were administrated on 9 weeks after operation.C,D and E group were treated by the differentdrugs lavage for 12 weeks.A and B group were given normal saline at the same time.Lumbar spine bone mineral densities （BMD） of rats were measured on pre-operation,before administration,6 weeks and 12 weeks after administration.All rats were sacrificed on 12 weeks after administration.Serum osteocalcin （BGP）,interleukin-6（IL-6） and Ca2＋ were measured.Bone histologywasobserved.Results After the treatment by simvastatin or androgen for 12 weeks,BMD of the group C and group Dwas significantlyhigher than that of group A（P 〈0.01）.After the treatment by simvastatin and androgen for 6 weeks,BMD of the group E was significantlyhigher than that of group A,C and D （P 〈 0.05）.The level of serum BGP in group Awassignificantlylowerthan that ingroup B （P 〈 0.05）and the level of serum BGP in group E was significantly higher than that in group B （P 〈 0.05）.The serum IL-6 in eachtreated group were significantly lower than thatin group A （P 〈 0.05）.Conclusion The combination of simvastatin and androgen could inhibit bone absorption and promote bone formation,which could improve the osteoporosis.