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李杰,范永升,丁兴红.基于“肾主骨”理论探讨解毒祛瘀滋阴方治疗糖皮质激素性骨质疏松的作用机制[J].,2023,43(7):846-850
基于“肾主骨”理论探讨解毒祛瘀滋阴方治疗糖皮质激素性骨质疏松的作用机制
Mechanism of Jiedu Quyu Ziyin Decoction in Treating Glucocorticoid-induced Osteoporosis Based on the Theory of Shen Dominating Bone
  
DOI:10.7661/j.cjim.20230531.083
中文关键词:  肾主骨  解毒祛瘀滋阴方  肾损伤  HPA轴  糖皮质激素性骨质疏松  中医
英文关键词:Shen dominating bone  Jiedu Quyu Ziyin Decoction  kidney injury  HPA axis  glucocorticoid-induced osteoporosis  Chinese medicine
基金项目:国家自然科学基金资助项目(No.81973778,No.81774179)
Author NameAffiliation
李杰,范永升,丁兴红 浙江中医药大学基础医学院(杭州 310053) 
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中文摘要:
      目的 基于“肾主骨”理论从“肾”的功能意义探讨解毒祛瘀滋阴方修复“肾”损伤治疗糖皮质激素性骨质疏松(GIOP)的作用机制。方法 将40只雌性C57BL/6小鼠随机分为对照组(Control)、模型组(Model)、解毒祛瘀滋阴方治疗组(JP)和阿仑膦酸钠治疗组(ALN),每组10只。Model组、JP组及ALN组给予地塞米松(5 mg/kg/d)肌注隔日给药造模,JP组及ALN组分别给予解毒祛瘀滋阴方[5 mg/(kg·d)]及阿仑膦酸钠混悬液[1.3 mg/(kg·d)]灌胃给药,连续12周。小鼠腿骨用Micro-CT扫描观察骨状况[骨密度(BMD)及骨体积分数(BV/TV)、平均骨小梁宽度(Tb.Th)、骨小梁数目(Tb.N)、平均骨小梁分离度(Tb.Sp)]指标及建立股骨远端平扫图像;ELISA法检测各组小鼠血促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质醇(CORT);测量肾脏重量并观察组织形态学变化。结果 与Control组比较,Model组小梁显著减少、结构变薄,BMD、BV/TV、Tb.Th、CRH、ACTH、CORT水平降低、肾脏重量下降(P<0.05,P<0.01),Tb.Sp、肾小球肥大指数、肾小球硬化指数升高(P<0.01)。与Model组比较,JP组及ALN组小梁数量及结构均有改善,BMD、BV/TV、Tb.N、CRH、ACTH、CORT水平升高,Tb.Sp下降(P<0.05,P<0.01),肾脏重量升高,肾小球肥大指数降低(P<0.05,P<0.01),同时JP组肾小球硬化指数降低(P<0.01)。结论 解毒祛瘀滋阴方可通过修复糖皮质激素导致的“肾”损伤来达到补“肾”治骨的效果,改善糖皮质激素诱导的骨量降低状态,增强骨强度,从而治疗GIOP。
英文摘要:
      Objective To investigated the mechanism of Jiedu Quyu Ziyin Decoction in the treatment of glucocorticoid-induced osteoporosis(GIOP) based on the theory of Shen dominating bone.Methods Totally 40 female C57BL/6 mice were randomly divided into control group,model group,Jiedu Quyu Ziyin Decoction group(JP group) and Alendronate group(ALN group),10 mice in each group.Model group,JP group and ALN group were given dexamethasone(5 mg·kg-1·d-1) intramuscular injection every other day for modeling.JP group and ALN group were given Jiedu Quyu Ziyin Decoction(15.6 g·kg-1·d-1) and alendronate sodium suspension(1.3 mg·kg-1·d-1) by intragastric administration for 12 weeks respectively.Micro-CT scan was used to observe the bone status [bone mineral density(BMD),bone volume fraction(BV/TV),mean trabecular width(Tb.Th),number of trabecular bone(Tb.N),and mean trabecular separation(Tb.Sp)] and establish the distal femur plain scan image.The levels of corticotropin releasing hormone(CRH),adrenocorticotropic hormone(ACTH) and cortisol(CORT)in blood were detected by ELISA.Kidney weight and histomorphological changes were observed.Results Compared with the control group,the trabecular structure of the model group was significantly reduced,the structure became thinner,the levels of BMD,BV/TV,Tb.Th,CRH,ACTH,CORT and kidney weight decreased(P<0.05,P<0.01); Tb.Sp,glomerular hypertrophy index and glomerular sclerosis index increased(P<0.01).Compared with the model group,the trabecular number and structure of JP group and ALN group were improved,BMD,BV/TV,Tb.N, CRH,ACTH,CORT levels increased,Tb.Sp decreased(P<0.05,P<0.01),kidney weight increased,glomerular hypertrophy index decreased(P<0.05, P<0.01),and glomerular sclerosis index decreased in the JP group(P<0.01).Conclusion Jiedu Quyu Ziyin Decoction can achieve the effect of tonifying Shen and treating bone byrepairing 'kidney' injury caused by glucocorticoid, improve the reduction of bone mass,enhance bone strength,and thus treat GIOP.
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