活骨灌注液不同给药途径对激素性股骨头坏死相关炎性因子表达的影响

Effects of Different Routes of Administration on the Expression of Steroid-induced Osteonecrosis of the Femoral Head-associated Inflammatory Factors by Huogu Perfusion Fluid

目的:观察活骨灌注液不同给药途径对兔激素性股骨头坏死(SONFH)的治疗作用,为临床治疗股骨坏死提供新的治疗方案。方法:雄性新西兰大白兔随机分为空白组(15只)和造模组(60只)。造模组行兔股骨头坏死动物造模后(采用Matsui造模方法,末次腹腔注射用甲泼尼龙琥珀酸钠4周后开始治疗)再随机分为4组:耳缘静脉组(E)、灌胃组(W)、外敷组(F)、模型组(M)各15只。空白组(K)正常饲养,不给予任何药物治疗。耳缘静脉组给予活骨灌注液10 mg/kg,1周2次;灌胃组给予活骨灌注液7.8 mg/kg,每日1次;外敷组给予双后肢上部内侧外敷透皮贴剂,每次7.5 g/贴,每3日1次。治疗12周后,采用苏木精-伊红染色观察股骨头病理学变化及MRI检查证明造模成功,采用ELISA法检测血清IL-1β,IL-6及IL-8水平。结果:ELISA法检测结果:模型组中的IL-1β,IL-6及IL-8含量测定相对正常组有明显增高,差异有统计学意义(P<0.01);与模型组相比,不同给药途径中,IL-1β,IL-6及IL-8蛋白含量均有不同程度的降低,差异有统计学意义(P<0.01)。苏木精-伊红染色观察显示:模型组股骨头软骨膜脱失,骨髓腔内脂肪细胞明显增多,关节腔内水肿,骨内压增高。活骨灌注液组方的不同给药途径均可以不同程度改变股骨头的病理变化,包括软骨层增生、骨小梁结构规整、软骨陷窝数量减少、骨髓腔内脂肪细胞明显减少、水肿及骨内压明显减轻。结论:活骨灌注液不同给药途径均能够对SONFH的病理变化起到治疗作用,活骨灌注液耳缘静脉给药方法对兔SONFH的治疗作用效果显著。

Objective:To observe the therapeutic effect of four different administration routes of living bone perfusion solution on steroid-induced necrosis of femoral head(SONFH)in rabbits,and to provide a new therapeutic scheme for clinical treatment of femoral necrosis.Methods:Male New Zealand white rabbits were randomly divided into two groups:blank group(n=15)and model group(n=60).The rabbits in the model group were randomly divided into 5 groups:auricular vein group(E),gastric perfusion group(W),external application group(F)and model group(M)with 15 animals each.The model of steroid-induced osteonecrosis of femoral head was established by Matsui,and the treatment began 4 weeks after the last intraperitoneal injection of methylprednisolone succinate sodium.The blank group(K)was raised normally and no drug treatment was given.The auricular vein was given live bone perfusion solution 10 mg/kg,twice a week,gastric perfusion group was given live bone perfusion fluid 7.8 mg/kg,once a day.The external application group was given transdermal patch on the upper and medial side of the upper hindlimb,Every 7.5 g/post,once every 3 d.After 12 weeks of treatment,the pathological and imaging changes of femoral head were observed by HE staining and electron microscope.The levels of serum IL-1β,IL-6,IL-8 were detected by ELISA.Results:The contents of IL-1β,IL-6,IL-8,in the model group were significantly higher than those in the normal group(P<0.01),and those in the model group were significantly higher than those in the normal group(P<0.01).HE staining observation showed that in the model group,perichondrium of femoral head was lost,adipocytes in bone marrow cavity increased significantly,intra-articular edema and intra-osseous pressure increased.The pathological changes of femoral head could be changed by different administration routes of Huogu perfusion solution,including cartilage layer hyperplasia,regular trabecular structure,reduction of cartilage lacunae,decrease of adipocytes in bone marrow cavity,and decrease of edema and intraosseous pressure.Conclusion:The results showed that different routes of administration of bone-activating perfusate could treat the pathological changes of SONFH,and the therapeutic effect of auricular vein administration of bone-activating perfusate on SONFH in rabbits was significant.