甲磺酸去铁胺促进去势骨质疏松大鼠颌骨缺损的修复  

Deferoxamine mesylate improves the repair of jaw bone defects in an ovariectomized rat model of osteoporosis

作　　者：田艾 李丽 肖天骄 康佳兵 湛济帆 韦艳 陈河林 Tian Ai;Li Li;Xiao Tianjiao;Kang Jiabing;Zhan Jifan;Wei Yan;Chen Helin(School of Stomatology,Guizhou Medical University,Guiyang 550004,Guizhou Province,China;Department of Prosthodontics and Implantology,Affiliated Stomatology Hospital,Guizhou Medical University,Guiyang 550004,Guizhou Province,China)

机构地区：[1]贵州医科大学口腔医学院,贵州省贵阳市550004 [2]贵州医科大学附属口腔医院口腔修复种植科,贵州省贵阳市550004

出　　处：《中国组织工程研究》2024年第20期3143-3149,共7页Chinese Journal of Tissue Engineering Research

基　　金：贵阳市科技计划项目基金资助(筑科[2018]1-82),项目负责人:田艾;国家自然科学基金(81760192,82260193),项目负责人:田艾。

摘　　要：背景:甲磺酸去铁胺(deferoxamine mesylate,DFO)是一种抗骨质疏松的潜在药物,具有铁螯合、血管再生、抗氧化等作用,近年来研究表明DFO的应用可扩展到组织再生工程领域。目的:以高铁干预去势大鼠模拟绝经后骨质疏松症患者体内铁蓄积状态,探讨DFO干预铁过载骨质疏松大鼠下颌骨缺损植骨后的修复效果。方法:首先构建铁蓄积去势骨质疏松模型,模型组大鼠行双侧卵巢切除术,第2周开始腹腔注射枸橼酸铁铵(90 mg/kg,每周2次,持续干预11周),假手术组大鼠去除卵巢周围部分脂肪,给予等量生理盐水干预11周。确认模型建立成功后,实验大鼠分为假手术组(n=6)、高铁去势组(n=6)和高铁去势DFO治疗组(n=6),于双侧下颌骨建立直径5 mm的骨缺损并植入Bio-Oss骨粉,术后第4天开始高铁去势DFO治疗组腹腔注射DFO(100 mg/kg,每周3次),假手术组及高铁去势组予以等量生理盐水干预,植骨术后2,12周取下颌骨、肝脏及血液样本,行肝脏及颌骨普鲁士蓝染色、血清铁蛋白ELISA检测体内各组织铁水平;苏木精-伊红染色、Masson染色观察骨缺损区炎症细胞浸润及早期成骨情况;抗酒石酸酸性磷酸酶染色观察破骨细胞分化情况;ELISA法检测血清中降钙素、Ⅰ型胶原C-末端肽水平;Micro-CT检测、苏木精-伊红染色观察中晚期成骨情况。结果与结论:①高铁去势组胫骨骨小梁数目减少,骨小梁排列稀疏;②与假手术组比较,植骨术后2周高铁去势组肝脏、颌骨及血清中铁水平明显升高,DFO干预后铁水平降低,差异均有显著性意义(P<0.05);③骨缺损修复早期,高铁去势组较假手术组有较多炎性细胞浸润,新生骨基质较少,Ⅰ型胶原纤维生成较少(P<0.05);DFO干预后炎性细胞浸润减少,少量新生骨基质生成,胶原纤维增加显著(P<0.05);④骨缺损修复中晚期,Micro-CT显示高铁去势组较假手术组新骨生成减少,DFO治疗后新生骨质增加(P<0.05);�BACKGROUND:Deferoxamine mesylate is a potential anti-osteoporosis drug with iron chelation,vascular regeneration,and antioxidant effects.Recent studies have shown that the application of deferoxamine mesylate can be extended to the field of tissue regeneration engineering.OBJECTIVE:To investigate whether deferoxamine mesylate can promote the repair effect of iron overload osteoporotic rats after bone grafting for mandibular bone defects by simulating the state of iron accumulation in patients with postmenopausal osteoporosis with high iron intervention in osteoporotic rats.METHODS:An iron accumulation ovariectomized osteoporosis model was firstly constructed.The model group underwent bilateral ovariectomy,and the intraperitoneal injection of ferric ammonium citrate(90 mg/kg,twice a week,for 11 weeks)was started in the 2nd week,while the sham-operated group had some fat around the ovaries removed and was given an equal amount of saline for 11 weeks.After the successful modeling,the experimental rats were divided into sham-operated group(n=6),high iron ovariectomtized group(n=6)and high iron ovariectomized deferoxamine mesylate treatment group(deferoxamine mesylate group,n=6).Bone defects of 5 mm in diameter were established in the rat’s bilateral mandibles and implanted with Bio-Oss bone powder.Intraperitoneal injection of deferoxamine mesylate(100 mg/kg,3 times a week)was started on postoperative day 4 in the deferoxamine mesylate group,and equal volume of saline was given in the sham-operated and high iron ovariectomized groups.The bone samples of the mandible,liver and blood were taken at 2 and 12 weeks after bone grafting for Prussian blue staining of the jaw and liver and ELISA detection of serum ferritin to detect iron levels in various body tissues;hematoxylin-eosin staining and Masson staining were performed to observe inflammatory cell infiltration and early osteogenesis in the bone defect area;tartrate resistant acid phosphatase staining was performed to observe osteoclast differentiation;ELISA was per

关 键 词：甲磺酸去铁胺 骨质疏松 铁 骨缺损 新骨生成 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R392