血管紧张素Ⅱ可促进小鼠激素诱导的缺血性股骨头坏死

Angiotensin Ⅱ promotes steroid-induced avascular necrosis of the femoral head in mice

背景:关于激素性股骨头坏死的发病机制的研究很多,但目前相关机制仍未阐述清楚。股骨头局部血运障碍被认为是股骨头坏死的一个重要原因。目的:观察血管紧张素Ⅱ对激素诱导的缺血性股骨头坏死的影响。方法:实验将Balb/c雄性小鼠随机分为3组:地塞米松联合血管紧张素Ⅱ组,将地塞米松置于饮水中(2 mg/L),实验开始第1天皮下植入胶囊渗透泵,按照0.28 mg/(kg·d)持续泵入血管紧张素Ⅱ共4周;地塞米松组,地塞米松用量、用法同地塞米松联合血管紧张素Ⅱ组;对照组正常饲养。全部动物饲养6周。结果与结论:①一般情况及病理改变显示,地塞米松联合血管紧张素Ⅱ组小鼠较其他两组体质量增长程度明显较低,血清总胆固醇水平、总三酰甘油水平、小鼠股骨头空骨陷窝率及骨小梁占有率(BV/TV)较其他2组明显升高(P <0.05),骨坏死程度更加明显;②免疫组织化学染色显示,地塞米松联合血管紧张素Ⅱ组骨保护素蛋白表达明显大于其他2组(P <0.05),破骨行为更活跃;③结果证实,血管紧张素Ⅱ能够明显促进小鼠激素诱导的股骨头坏死。

BACKGROUND: There are many studies on the pathogenesis of steroid-induced avascular necrosis of the femoral head, but the relevant mechanisms remain unclear. Local obstruction of blood flow to the femoral head is an important cause of avascular necrosis of the femoral head. OBJECTIVE: To investigate the effect of angiotensin Ⅱ on avascular necrosis of the femoral head. METHODS: Male Balb/c mice were randomly divided into three groups. In the dexamethasone plus angiotensin Ⅱ group, 2 mg/L dexamethasone was added in drinking water, subcutaneous implantatian with osmotic pump capsules began on the first day, followed by pumping with 0.28 mg/(kg?d) angiotensin Ⅱ for 4 weeks. Dexamethasone group dosage and usage were the same as dexamethasone plus angiotensin Ⅱ group. Control group had normal feed. All mice were fed for 6 weeks. RESULTS AND CONCLUSION:(1) General condition and pathological changes showed that compared with the dexamethasone and control groups, the body mass increase was significantly decreased, and the serum total cholesterol, total triglyceride, empty lacunae rate and bone volume/tissue volume were significantly increased in the dexamethasone plus angiotensin Ⅱ group(P < 0.05), and the degree of osteonecrosis was more obvious.(2) Immunohistochemical results showed that the osteoprotegerin protein expression level in the dexamethasone plus angiotensin Ⅱ group was significantly higher than that in the other two groups(P < 0.05), indicating that the osteoclast was more active.(3) In summary, angiotensin Ⅱ can obviously promote steroid-induced avascular necrosis of the femoral head in mice.