肾虚血瘀型Kümmell病大鼠模型的构建与验证OA
Establishment and characterization of a rat model simulating Kümmell disease with kidney deficiency and blood stasis syndromes
目的 建立评价肾虚血瘀型Kümmell病(Kümmell disease,KD)的动物模型以探究其潜在治疗靶点与作用机制.方法 将40只SD大鼠随机分为正常组、骨质疏松组、假手术组、对照组与模型组.模型组行卵巢切除术诱导肾虚状态,2个月后于尾椎制造骨缺损模型,施加4周机械应力.骨缺损术后1周皮下注射盐酸肾上腺素诱导血瘀证.对照组行卵巢切除与骨缺损术,注射0.9％氯化钠溶液.监测各组体温、体质量、摄食饮水量及舌象变化.建模结束后进行行为学观察,并行影像学、血液流变学及组织病理学检测.结果 模型组较假手术组及对照组呈现体温升高、体质量减轻、摄食减少、舌质紫暗伴舌下络脉迂曲、毛发枯槁、精神萎靡及运动障碍.影像学显示模型组皮质变薄、骨小梁稀疏断裂、椎体内真空裂隙征.血液学检测提示模型组全血黏度(低/中/高切)及血浆黏度显著升高,纤维蛋白原上升,凝血酶时间、凝血酶原时间及活化部分凝血活酶时间缩短;血清钙磷降低,骨转换标志物升高;甲状腺激素及雌二醇水平较假手术组显著降低.组织病理学显示模型组骨小梁结构破坏,新生骨低于对照组.结论 卵巢切除联合肾上腺素诱导及机械应力干预可成功构建肾虚血瘀证候的KD大鼠模型,为其机制研究和治疗提供了有效的平台.
Objective To establish an animal model of Kümmell disease(KD)characterized by kidney deficiency and blood stasis,providing a foundation for exploring therapeutic targets and underlying pathophysiological mechanisms.Methods Forty SD rats were randomly assigned to normal,osteoporosis(OP),sham operation(Sham),control,and model(KD)groups.Rats in the KD group underwent ovariectomy to induce kidney deficiency,followed 2 months later by creation of coccygeal bone defects and application of mechanical stress for 4 weeks.One week after bone defect surgery,subcutaneous injections of adrenaline hydrochloride were administered to induce blood stasis.Control group rats underwent ovariectomy and bone defect surgery but received 0.9％sodium chloride solution.During the experiment,body temperature,body mass,food and water intake,and tongue characteristics were monitored.After model establishment,behavioral assessments,imaging analyses,hemorheological testing,and histopathological examinations were performed.Results Compared with the sham and control groups,KD group rats showed elevated body temperature,mass loss,reduced food intake,purple tongues with tortuous sublingual veins,dry fur,lethargy,and impaired mobility.Imaging revealed cortical thinning,sparse and fractured trabeculae,and vacuum cleft signs in vertebral bodies.Hemorheological evaluation showed significantly increased whole blood viscosity at low,medium,and high shear rates,increased plasma viscosity,elevated fibrinogen levels,and shortened thrombin time,prothrombin time,and activated partial thromboplastin time.Serum calcium and phosphorus levels decreased,while bone turnover markers increased.Thyroid hormone and estradiol levels were significantly lower than in the sham group.Histopathological examination showed KD group disrupted trabecular structure and reduced new bone formation compared with the control group.Conclusions Combined ovariectomy,adrenaline-induced blood stasis,and mechanical stress successfully establish a rat model of KD with kidney deficiency and blood stasis syndrome,providing a useful platform for mechanistic studies and therapeutic evaluation.
王东平;张顺聪;刘畅;朱一豪;古淑灵;成品莹;高逸涵;冯紫淇;李子彬;李永贤
广州中医药大学第一临床医学院,广州 510405广州中医药大学第一附属医院脊柱微创科,广州 510405||广东省中医临床研究院,广州 510440广州中医药大学第一临床医学院,广州 510405广州中医药大学第一临床医学院,广州 510405广州中医药大学针灸康复临床医学院,广州 510006广州中医药大学第五临床医学院,广州 510095广州中医药大学第二临床医学院,广州 510405广州中医药大学第二临床医学院,广州 510405广州中医药大学第一临床医学院,广州 510405广州中医药大学第一附属医院脊柱微创科,广州 510405||广东省中医临床研究院,广州 510440
生物科学
Kümmell病肾虚血瘀动物模型病证结合卵巢摘除骨质疏松症
Kümmell diseasekidney deficiency and blood stasisanimal modelcombination of disease and syndromeovariectomyosteoporosis
《中国实验动物学报》 2026 (4)
519-530,12
广东省中医药管理局(20241091),中华中医药学会青年人才提升项目(2022-QNRC2-B11),广东省中医药管理局科研项目(20251106).Funded by the Administration of Traditional Chinese Medicine of Guangdong Province,China(20241091),Chinese Society of Traditional Chinese Medicine Youth Talent Lifting Project(2022-QNRC2-B11),Guangdong Provincial Administration of Traditional Chinese Medicine Research Project(20251106).
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