尿激酶和阿司匹林联合应用对股骨头缺血坏死微血管内凝血的干预作用

The Early Intervention on Prethrombolic State of Avascular Necrosis of the Femoral Head in Rabbits with Combined Use of Urokinase and Aspirin

目的制造兔股骨头缺血坏死(ANFH)模型;验证PTS与ANFH的密切关系,并探讨尿激酶与阿司匹林联合预防兔激素性股骨头坏死的作用。方法选用健康日本大耳白兔36只,随机均分为3组。第I组为模型组:先分2次间隔2周分别按10ml/kg量静脉注射马血清,第2次注射马血清2周后,再连续肌注甲基强的松龙10mg/kg.d,共7天,之后口服强的松1.25mg/kg.d至实验完。第Ⅱ组为治疗组(马血清和激素加药物预防):按第I组方法用马血清和激素;另外,第一个月每周2次静脉注射尿激酶8万U/kg/d,之后灌服阿司匹林5mg/kg.d至实验结束。第Ⅲ组为对照组,每日于耳缘静脉注射生理盐水2 ml。分期分批取血采用放射免疫法测定内皮素(ET-1)、免疫比浊法测定抗凝血酶-Ⅲ(AT-Ⅲ)和D-二聚体(D-dimer)的变化。股骨头组织取样石蜡切片作HE染色;冰冻切片Sudan染色。结果3个月时,模型组AT-Ⅲ[(61.44±5.05)mg/L]较治疗组和对照组降低;D-dimer[(0.53±0.19)μg/ml]和ET-1[(47.84±12.09)pg/L]较治疗组和对照组升高。模型组骨坏死的发生率100%,治疗组骨坏死的发生率25%,显著低于模型组。对照组未见骨坏死。结论激素性股骨头坏死的发病与高凝状态有关,联合应用尿激酶与阿司匹林能有效预防兔激素性股骨头坏死的发生。

Objective To produce animal model of ANFH with horse serum added glucocorticoid and to investigate the role of prethrombotic state and intravascular coagulation to induce ANFH. In addition, to investigate the effects of Urokinase plus Aspirin on the prevention of the avascular necrosis of femoral bead （ANFH） in rabbits. Methods Sixty adult Japanese white rabbits were chosen and randomly divided into three groups. Group I（model group） were given intra- vascular injection of horse serum at dose 10ml/kg at intervals of 14 days. Two weeks after the end of the immunization, the rabbits were received intramuscular injection of ethylprednisolone at a dose of 10mg/kg · d for 7 days. Then, the ani- mal received prednisolone at a dose of 1.25mg/kg · d mixed with food until the end of the study. Group 11 （treatment group） were given horse serum and glucocorticoid following the same method of group I , In addition, the rabbits were received intravascular injection of Urokinase at a dose of 80,000U/kg · d for 30 days. Then, the animal received Aspirin orally at a dose of 5mg/kg · d until the end of the study. Group Ⅲ were control group. The animals in three groups were sacrificed in batches 1, 3 and 6 months after the procedures. The changes of histology in the femoral head were observed by means of HE staining, Sudan staining. In addition, Endothelins-I were examined by means of radioimmunoassay. An- tithrombin-Ⅲ and D-dimer were examined by means of immunoturbidimetry. Results In the third month, the group showed that AT-Ⅲ （61.44±5.05mg/L）was lower than treatment and controls; ET-I（47.84± 12.09pg/L）and D-dimer （0. 53±0.19μg/ml）began to rise compared with treatment and controls respectively. The incidence of osteoneerosis in the model group was 100% ; the incidence of osteonecrosis in the treatment group （250%） was significantly lower than in the model group and no osteonecrosis was observed in the control group. Conclusion Hypercoagulability is a risk factor for osteonecrosis. The combined use of Urokinase and Aspirin can prevents avascular necrosis of the femoral head in rabbits.