高磷联合腺嘌呤饮食诱导大鼠高转化型肾性骨病模型的建立与分析  

Establishment and analysis of the rat high bone turnover renal osteopathy model induced by high phosphorus diet containing adenine

作　　者：张豪[1] 孟彦[2,3] 金小冬 陈珺[1] 李英彬[1] 黄韧[4] 左力[2,3] 李青南[1] 

机构地区：[1]广东药学院生命科学与生物制药学院新药功能研究中心,广东省生物技术候选药物研究重点实验室,广州510006 [2]北京大学第一医院肾内科 [3]北京大学肾脏病研究所,教育部肾脏病重点实验室,教育部慢性肾脏病的预防与治疗重点实验室,北京100088 [4]广东省实验动物监测所 广东省实验动物重点实验室

出　　处：《中国骨质疏松杂志》2014年第5期485-489,共5页Chinese Journal of Osteoporosis

摘　　要：目的探讨高磷联合腺嘌呤制作大鼠慢性肾脏病(chronic kidney disease,CKD)模型诱导的骨矿代谢异常。方法雄性3月龄SD大鼠30只,随机分成三组:基础组(Basal)、对照组(Control)、慢性肾病组(CKD),实验持续6周。所有大鼠先饲养两周以适应环境,Basal在实验开始时处死;Control组给予高磷(1.03%)饮食;CKD组前四周给予腺嘌呤(0.75%)和高磷(1.03%)饮食,后两周给予不含腺嘌呤的高磷(1.03%)饮食。所有动物在处死前进行体内双荧光标记。实验结束时,取左侧胫骨上段(proximal tibia metaphometry,PTM)不脱钙包埋,并采用骨组织形态计量学方法分析。结果与Basal组相比:6周高磷饮食的Control组大鼠骨组织未出现静态参数、生长板参数的变化;而动态参数显示矿化沉积率(MAR)、类骨质体积百分数(%OV/BV)明显增加,矿化延迟时间(MLT)明显减少。与Control组相比:CKD组骨小梁面积百分数(%Tb.Ar)、骨小梁数量(Tb.N)显著降低,骨小梁分离度(Tb.Sp)显著性升高;荧光周长百分率(%L.Pm)、矿化沉积率(MAR)、骨形成率(BRF/TV、BRF/BS、BRF/BV)、类骨质周长百分数(%O.Pm)、类骨质面积百分数(%OV/BV)、每毫米成骨细胞数量(Ob.N)、成骨细胞贴壁周长(%Ob.S.Pm)、每毫米破骨细胞数(Oc.N)、破骨细胞贴壁周长(%Oc.S.Pm)、明显升高,MLT与髙磷对照组比无变化,与Basal组比也减少。生长板参数显示:生长板宽度(G.P.Wi)、纵向生长率(L.G.R)明显减少,但是退行细胞高度(D.C.H)没有改变。结论 CKD模型导致骨的变化表现为明显的骨高转换模型,既促进骨形成,也促进骨吸收;最终骨量减少,说明骨吸收大于骨形成。生长板参数G.P.Wi和L.G.R减少,说明此模型对软骨下成骨有抑制作用。Objective To investigate the bone metabolism disorders in established rat chronic kidney disease （ CKD） model, which was induced by high phosphorus diet containing adenine.Methods Thirty 3-month male SD rats were randomly divided into three groups：Basal group , Control group , and CKD group .The whole experiment lasted for 6 weeks .All the rats were fed for 2 weeks to adapt the environment .Then, rats in Basal group were executed at the beginning of the experiment .Rats in Control group were fed＆amp;nbsp;with high phosphorus （ 1.03%） diet.And rats in CKD group were fed with high phosphorus （ 1.03%） diet containing adenine （0.75%） for 4 weeks.The rats were then fed with high phosphorus （1.03%） diet without adenine for 2 weeks.Before execution, all the rats were subcutaneously injected with calcein （10 mg/kg）.The left tibias （proximal tibia metaphometry, PTM） were embedded without decalcification and analyzed with histomorphometrical method .Results Compared with that in Basal Group, after 6-week high phosphorous diet, no change of static parameters and growth plate parameters were observed in Control group.Also, the dynamic parameters showed that mineral apposition rate （ MAR ） and osteoid volume （%OV/BV ） increased significantly, but mineral lag time （ MLT） decreased markedly.Compared with that in Control group, the percent trabecular area （%Tb.Ar） and the trabecular number （ Tb.N） decreased markedly in CKD group, while the trabecular separation （ Tb.Sp） increased significantly.The dynamic parameters showed that the percent labeled perimeter （%L.Pm）, mineral apposition rate （MAR）, bone formation rate （ BFR/TV, BRF/BS, and BRF/BV） , the percent osteoid perimeter （%O.Pm） , the percent osteoid area （%OV/BV） , osteoblast number per mm （Ob.N）, the percent osteoblast surface perimeter （%Ob.S.Pm）, the osteoclast number per mm （Oc.N）, and the percent osteoclast surface perimeter （%Oc.S.Pm） increased significantly.MLT in CKD group

关 键 词：高磷饮食 腺嘌呤 高转化骨病 慢性肾脏病 肾性骨病模型 

分 类 号：R68[医药卫生—骨科学]