睾酮干预雄兔膝骨关节炎软骨中胰岛素样生长因子1的表达

Effects of testosterone on expression of insulin-like growth factor 1 in cartilage of knee joints with osteoarthritis in male rabbits

背景:睾酮对骨关节炎的作用尚无一致的观点,其调节软骨代谢的作用鲜有文献报道。目的:观察睾酮对膝骨关节炎雄兔关节软骨中胰岛素样生长因子1表达的影响。方法:24只雄兔随机分成4组,采用改良Hulth法建立右膝骨关节炎模型;假去势组不切除睾丸,其余3组切除双侧睾丸。第8周末处死假去势组和去势8周组兔取材。第9周开始,激素组肌注生理剂量十一酸睾酮(6mg/kg,2周1次),去势16周组正常喂养,并于16周末处死并取材。结果与结论:大体和组织学观察显示各组兔膝关节软骨的病变程度为假去势组优于去势8周组,激素组优于去势16周组。免疫组化染色显示胰岛素样生长因子1在所有兔膝关节软骨中均有表达,阳性细胞个数假去势组高于去势8周组(P<0.05),激素组高于去势16周组(P<0.05),去势8周组与去势16周组差异无显著性意义(P>0.05)。说明睾酮可通过上调去势雄兔关节软骨中胰岛素样生长因子1的表达,延缓软骨退变。

BACKGROUND：The effects of testosterone on osteoarthritis（OA） remain controversial.The regulatory effects of testosterone on cartilage metabolism have been rarely reported.OBJECTIVE：To investigate the effects of testosterone on insulin-like growth factor 1（IGF-1） expression in cartilage of knee joints with osteoarthritis in male rabbits.METHODS：Twenty-four male rabbits were established into OA models with Hulth method on the right knee joints and then randomly divided into four groups：non-castrated,castrated,testosterone and model.In the non-castrated group,testis was not removed.In the other three groups,bilateral testes were removed.At the end of the 8th week,rabbits in the non-castrated group and castrated for 8 weeks group were sacrificed for sample harvesting.From the 9th week,physiological dose of testosterone undecanoate（6 mg/kg,once every 2 weeks） was intramuscularly injected into the rabbits from the testosterone group.The castrated for 16 weeks group rabbits were normally raised.At the end of 16th week,rabbits from the testosterone and castrated for 16 weeks groups were sacrificed for sample harvesting.RESULTS AND CONCLUSION：Gross and histological observation results showed that the lesion degree of knee joint cartilage was more severe in the non-castrated group than in the castrated group,in the testosterone group than in the castrated for 16 weeks group,but there was no obvious difference between castrated for 8 weeks group and castrated for 16 weeks group.Immunohistochemistry results showed that IGF-1 expression was observed in the knee joint cartilage of all rabbits.IGF-1-positive cells were significantly more in the non-castrated group than in the castrated for 8 weeks group（P 0.05）,and they were also significantly more in the testosterone group than in the castrated for 16 weeks group（P 0.05）,and there was no significant difference between castrated for 8 weeks group and castrated for 16 weeks group（P 0.05）.These findings suggest that testosterone can postpone cartilage degeneration by up-regulating IGF-1 expression in knee joint cartilage of castrated male rabbits.