摘要
目的探讨鹿瓜多肽注射液与前列地尔注射液联合治疗成年大鼠股骨头坏死的效果及机制。方法将24只14周龄雄性成年大鼠随机分为对照组、模型组、鹿瓜多肽组、联合组,每组6只。对照组大鼠右后肢仅行假手术,其余3组大鼠右后肢制备创伤性股骨头坏死模型;模型组不进行治疗,鹿瓜多肽组大鼠于术后2 d开始腹腔注射鹿瓜多肽注射液1.44 mg·kg^(-1),联合组大鼠于术后2 d腹腔注射前列地尔注射液0.69μg·kg^(-1)和鹿瓜多肽注射液1.44 mg·kg^(-1),持续20 d。记录治疗过程中大鼠一般状况。苏木精-伊红染色观察股骨头显微形态学,免疫组织化学法检测股骨头中骨形态发生蛋白(BMP)-2和BMP-7表达,酶联免疫吸附法检测股骨头中碱性磷酸酶水平。结果术后各组大鼠均出现活动速度、活动总距离、自主活动次数减少和行走跛行、肢体活动对称性降低等表现,症状减轻或消失顺序依次为对照组、联合组、鹿瓜多肽组和模型组。模型组大鼠股骨头骨小梁排列紊乱稀疏、断裂较多,可见较多骨小梁碎片,空骨陷窝多见,骨细胞数量减少,骨髓水肿,髓内造血细胞减少,脂肪细胞肥大增生,有脂肪栓子及血栓形成等典型股骨头坏死改变。鹿瓜多肽组大鼠骨小梁排列结构尚正常,骨小梁细长且断裂,可见空骨陷窝较多、小血管增生,骨细胞数量多于模型组。联合组大鼠骨小梁结构正常,断裂少,空骨陷窝少见,小血管增生多见,骨细胞数量和血管数量多于鹿瓜多肽组。模型组大鼠股骨头BMP-2和BMP-7表达水平显著低于对照组(P<0.05);鹿瓜多肽组和联合组大鼠股骨头BMP-2和BMP-7表达水平显著高于模型组(P<0.05);联合组大鼠股骨头BMP-2和BMP-7表达水平显著高于鹿瓜多肽组(P<0.05)。对照组、鹿瓜多肽组和联合组大鼠右侧股骨头碱性磷酸酶水平显著高于模型组(P<0.05);对照组和联合组大鼠右侧股骨头碱性磷酸酶水平显著高于鹿瓜多肽组(P<0.05);对照组与联合组大鼠右侧股骨头碱性磷酸酶水平比较差异无统计学意义(P>0.05)。结论鹿瓜多肽注射液联合前列地尔注射液对创伤性股骨头坏死的治疗效果优于单独使用鹿瓜多肽注射液,其机制可能与2种药物发挥协同作用有关。
Objective To investigate the effect and mechanism of cervus and cucumis polypeptide injection combined with alprostadil injection in the treatment of femoral head necrosis in adult rats.Methods Twenty-four 14-week-old male adult rats were randomly divided into control group,model group,cervus and cucumis polypeptide group,and combined group,with 6 rats in each group.The right hind limb of the rats in the control group was only sham-operated,and the right hind limb of the rats in the remaining three groups were replicated in the traumatic femoral head necrosis model;No treatment was performed in the model group.Rats in the cervus and cucumis polypeptide group were intraperitoneally injected with cervus and cucumis polypeptide injection 1.44 mg·kg^(-1) starting at 2 d postoperatively,while rats in the combined group were intraperitoneally injected with alprostadil injection 0.69μg·kg^(-1),and cervus and cucumis polypeptide injection 1.44 mg·kg^(-1) for 20 d postoperatively.The general conditions of the rats were recorded during the treatment process.Hematoxylin and eosin staining was used to observe the microscopic morphology of the femoral head,immunohistochemistry was used to detect the expression of bone morphogenetic protein(BMP)-2 and BMP-7 in the femoral head,and alkaline phosphatase level was detected in the femoral head by enzyme-linked immunosorbent assay.Results After the operation,the rats in the all groups showed reduced activity speed,total distance of activity,number of voluntary activities,walking lameness,and symmetry of limb activities.The order of symptom reduction or disappearance was as follows:control group,combined group,cervus and cucumis polypeptide group,and model group.In the model group,the trabecular arrangement of the femoral head was disorganized and sparse,with more fractures,trabecular fragments,empty bone lacunae,reduced number of osteocytes,marrow edema,decreased intramedullary hematopoietic cells,hypertrophy and hyperplasia of adipocytes,as well as fat embolisms and thrombus formation.Typical changes indicative of femoral head necrosis were observed in the model group.In the cervus and cucumis polypeptide group,the bone trabecular structure was normal,with elongated and broken trabeculae,more empty bone lacunae,small blood vessel hyperplasia,and a higher number of osteocytes compared to the model group.For the combined group,the bone trabecular structure was normal,with fewer fractures,empty bone lacunae,increased small blood vessel hyperplasia,and a higher number of osteocytes and blood vessels compared to the cervus and cucumis polypeptide group.The expression levels of BMP-2 and BMP-7 in the femoral head of rats in the model group were significantly lower than those in the control group(P<0.05).In the cervus and cucumis polypeptide group and the combined group,the expression levels of BMP-2 and BMP-7 were significantly higher than those in the model group(P<0.05).In the combined group,the expression levels of BMP-2 and BMP-7 were significantly higher than those in the cervus and cucumis polypeptide group(P<0.05).The level of alkaline phosphatase in the right femoral head of rats in the control group,cervus and cucumis polypeptide group,and combined group was significantly higher than that in the model group(P<0.05).The level of alkaline phosphatase in the control group and the combined group was significantly higher than that in the cervus and cucumis polypeptide group(P<0.05).There was no statistically significant difference in the alkaline phosphatase level in the right femoral head of rats between the control group and the combined group(P>0.05).Conclusion Cervus and cucumis polypeptide injection combined with alprostadil injection can be more effective than cervus and cucumis polypeptide injection alone in the treatment of traumatic femoral head necrosis,and the mechanism may be related to the synergistic effect of the two drugs.
作者
张向东
邵锋
千智斌
ZHANG Xiangdong;SHAO Feng;QIAN Zhibin(Department of Orthopedics,Zhoukou Central Hospital,Zhoukou 466099,Henan Province,China;Department of Orthopedics,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,Henan Province,China;School of Basic Medical Sciences,Xinxiang Medical University,Xinxiang 453003,Henan Province,China)
出处
《新乡医学院学报》
2025年第8期619-624,共6页
Journal of Xinxiang Medical University
基金
河南省科技厅重点攻关项目(编号:102102310156)。
关键词
鹿瓜多肽注射液
前列地尔注射液
股骨头坏死
大鼠
cervus and cucumis polypeptide injection
alprostadil injection
femoral head necrosis
rats
