【摘要】：目的:通過蔗糖鐵誘導(dǎo)去卵巢兔鐵蓄積狀態(tài),并建立鐵蓄積兔骨質(zhì)疏松性骨折(OPF)模型,研究鐵蓄積OPF愈合過程中血清Sclerostin表達(dá)的變化規(guī)律及意義,為通過干預(yù)血清Sclerostin水平防治鐵蓄積OPF提供理論依據(jù),并為鐵蓄積骨質(zhì)疏松的實(shí)驗(yàn)研究提供動(dòng)物模型基礎(chǔ)。方法:40只5月齡的新西蘭雌兔隨機(jī)分為對照組(10只)、去勢組(10只)和模型組(20只);去勢組和模型組切除雙側(cè)卵巢,對照組僅切除卵巢周圍部分脂肪;1周后模型組予耳緣靜脈注射蔗糖鐵(20mg/kg,每周1次,共12周),對照組和去勢組以相同頻次注射等量生理鹽水;各組分別于術(shù)前1天、術(shù)后4周、8周、12周、16周、20周、24周檢測血清1型前膠原氨基末端肽(P1NP),1型膠原羥基末端肽(CTX)及血清鐵蛋白(SF)水平,并行腰椎骨密度(BMD)測量。24周后將建立的鐵蓄積兔OP模型(模型組)隨機(jī)分為鐵蓄積非骨折組和鐵蓄積骨折組,每組10只;鐵蓄積骨折組通過手術(shù)造成左側(cè)橈骨遠(yuǎn)端骨折,鐵蓄積非骨折組僅切開皮下組織至暴露橈骨;每組分別于術(shù)前1天、術(shù)后1天、3天、7天、14天、21天、28天檢測血清P1NP,CTX,Sclerostin及SF水平,鐵蓄積骨折組于術(shù)后1天、3天、7天、14天、21天、28天進(jìn)行X光照射取片。結(jié)果:(1)所有動(dòng)物注射蔗糖鐵后均未出現(xiàn)不良反應(yīng)或致死情況;(2)模型組SF水平在造模后8周、12周、16周、20周及24周均明顯高于對照組(P0.05);(3)模型組與去勢組血清P1NP,CTX水平在造模后12周、16周、20周及24周均明顯高于對照組(P0.05);模型組血清P1NP,CTX水平在造模后20周及24周均明顯高于去勢組(P0.05);(4)模型組與去勢組腰椎BMD丟失百分率均在造模后第24周超過25%(P0.05),分別為33.40%、25.92%;(5)鐵蓄積骨折組血清Sclerostin水平在骨折后1天、3天、7天、14天、21天、28天均較鐵蓄積非骨折組明顯下降(P0.05);(6)鐵蓄積骨折組骨痂生長過程中始終伴隨著血清Sclerostin水平的下降(P0.05),且在骨折后14天達(dá)到最低值(34.72ng/ml),Sclerostin與骨痂生長評(píng)分呈負(fù)相關(guān)性(r=-0.746,P0.05);(7)在整個(gè)骨折愈合過程中,鐵蓄積骨折組的血清Sclerostin及CTX水平變化均呈下降趨勢,血清P1NP水平則呈上升趨勢;但SF水平無明顯變化,Sclerostin與SF無相關(guān)性(r=-0.152,P0.05)。結(jié)論:(1)蔗糖鐵結(jié)合去卵巢手術(shù)可成功建立鐵蓄積兔OP模型,其骨量丟失程度較單純?nèi)莘ń⒌腛P模型嚴(yán)重。(2)鐵蓄積OPF愈合早期即開始出現(xiàn)血清Sclerostin水平的下調(diào),且該下調(diào)狀態(tài)始終伴隨鐵蓄積OPF愈合的全程。(3)血清Sclerostin水平的下調(diào),可能發(fā)揮促進(jìn)鐵蓄積OPF愈合的作用。
[Abstract]:Objective: to establish a (OPF) model of osteoporotic fracture induced by sucrose iron in ovariectomy rabbits, and to study the changes and significance of serum Sclerostin expression during the healing of iron accumulation OPF. It provides a theoretical basis for the prevention and treatment of iron accumulation OPF by interfering with serum Sclerostin level, and provides an animal model basis for the experimental study of iron accumulation osteoporosis. Methods: forty 5-month-old New Zealand female rabbits were randomly divided into three groups: control group (n = 10), ovariectomized group (n = 10) and model group (n = 20), ovariectomized group (n = 10) and model group (n = 20), ovariectomized group (n = 10) and control group (n = 20). One week later, the model group was injected with sucrose iron (20 mg 路kg ~ (- 1) intravenously (once a week for 12 weeks). The control group and the castrated group were injected with the same amount of saline at the same frequency. Serum levels of P1NP, (CTX) and (SF) were measured 1 day before operation, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks after operation, respectively. The OP model of iron accumulation rabbits (model group) was randomly divided into iron accumulation non-fracture group and iron accumulation fracture group with 10 rabbits in each group. The distal radius fracture of the left side was caused by operation in the iron accumulation fracture group, and only the subcutaneous tissue was cut open to the exposed radius in the iron accumulation non-fracture group. The levels of serum P1NP, CTX, Sclerostin and SF in each group were measured 1 day before operation, 1 day, 3 days, 7 days, 14 days, 21 days after operation, and 1 day, 3 days, 7 days, 14 days and 21 days after operation. The films were taken by X-ray irradiation for 28 days. Results: (1) No adverse reaction or death occurred in all animals after injection of iron sucrose, (2) the level of SF in the model group was significantly higher than that in the control group at 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks after injection (P0.05). (3) the levels of serum P1NPand CTX in the model group and castrated group were significantly higher than those in the control group at 12 weeks, 16 weeks, 20 weeks and 24 weeks after modeling (P 0.05). The levels of serum P1NPand CTX in the model group were significantly higher than those in the ovariectomized group at 20 and 24 weeks after the establishment of the model (P0.05). (4) the percentage of BMD loss in lumbar vertebrae of model group and castrated group was more than 25% at the 24th week after modeling (P0.05), 33.40% and 25.92%, respectively. (5) the serum Sclerostin level in the iron accumulation fracture group was significantly lower than that in the iron accumulation non-fracture group at 1 day, 3 days, 7 days, 14 days, 21 days and 28 days after fracture (P 0.05). (6) the level of serum Sclerostin was always decreased during the growth of eschar in the iron accumulation fracture group (P 0.05), and reached the lowest value on the 14th day after fracture (34.72ng/ml), Sclerostin was negatively correlated with eschar growth score (r 鈮，

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