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铁蓄积兔OPF愈合过程中血清Sclerostin表达变化及意义

发布时间:2019-05-09 18:54
【摘要】:目的:通过蔗糖铁诱导去卵巢兔铁蓄积状态,并建立铁蓄积兔骨质疏松性骨折(OPF)模型,研究铁蓄积OPF愈合过程中血清Sclerostin表达的变化规律及意义,为通过干预血清Sclerostin水平防治铁蓄积OPF提供理论依据,并为铁蓄积骨质疏松的实验研究提供动物模型基础。方法:40只5月龄的新西兰雌兔随机分为对照组(10只)、去势组(10只)和模型组(20只);去势组和模型组切除双侧卵巢,对照组仅切除卵巢周围部分脂肪;1周后模型组予耳缘静脉注射蔗糖铁(20mg/kg,每周1次,共12周),对照组和去势组以相同频次注射等量生理盐水;各组分别于术前1天、术后4周、8周、12周、16周、20周、24周检测血清1型前胶原氨基末端肽(P1NP),1型胶原羟基末端肽(CTX)及血清铁蛋白(SF)水平,并行腰椎骨密度(BMD)测量。24周后将建立的铁蓄积兔OP模型(模型组)随机分为铁蓄积非骨折组和铁蓄积骨折组,每组10只;铁蓄积骨折组通过手术造成左侧桡骨远端骨折,铁蓄积非骨折组仅切开皮下组织至暴露桡骨;每组分别于术前1天、术后1天、3天、7天、14天、21天、28天检测血清P1NP,CTX,Sclerostin及SF水平,铁蓄积骨折组于术后1天、3天、7天、14天、21天、28天进行X光照射取片。结果:(1)所有动物注射蔗糖铁后均未出现不良反应或致死情况;(2)模型组SF水平在造模后8周、12周、16周、20周及24周均明显高于对照组(P0.05);(3)模型组与去势组血清P1NP,CTX水平在造模后12周、16周、20周及24周均明显高于对照组(P0.05);模型组血清P1NP,CTX水平在造模后20周及24周均明显高于去势组(P0.05);(4)模型组与去势组腰椎BMD丢失百分率均在造模后第24周超过25%(P0.05),分别为33.40%、25.92%;(5)铁蓄积骨折组血清Sclerostin水平在骨折后1天、3天、7天、14天、21天、28天均较铁蓄积非骨折组明显下降(P0.05);(6)铁蓄积骨折组骨痂生长过程中始终伴随着血清Sclerostin水平的下降(P0.05),且在骨折后14天达到最低值(34.72ng/ml),Sclerostin与骨痂生长评分呈负相关性(r=-0.746,P0.05);(7)在整个骨折愈合过程中,铁蓄积骨折组的血清Sclerostin及CTX水平变化均呈下降趋势,血清P1NP水平则呈上升趋势;但SF水平无明显变化,Sclerostin与SF无相关性(r=-0.152,P0.05)。结论:(1)蔗糖铁结合去卵巢手术可成功建立铁蓄积兔OP模型,其骨量丢失程度较单纯去势法建立的OP模型严重。(2)铁蓄积OPF愈合早期即开始出现血清Sclerostin水平的下调,且该下调状态始终伴随铁蓄积OPF愈合的全程。(3)血清Sclerostin水平的下调,可能发挥促进铁蓄积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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