甲状旁腺激素对双足鼠脊柱侧凸进展的影响

Effect of Parathyroid Hormone in an Asymmetric Force Bipedal Rat Scoliosis Model

目的探讨甲状旁腺激素(parathyroid hormone,PTH)对双足直立鼠脊柱侧凸进展的影响。方法 60只SD大鼠分为:双足鼠组、拴系-双足鼠组和PTH干预组。采取截除大鼠尾部及双前肢的方式建立双足鼠模型;在上述基础上,丝线拴系左侧肩胛下角与骨盆髂冀,建立拴系-双足鼠模型;PTH干预组即是在拴系-双足鼠模型基础上给予20μg/kg·d甲状旁腺激素皮下注射。造模后第8周末时,剪断栓系缝线,造模后第12周末时,处死大鼠。每4周拍摄脊柱正位X线全长片,观察侧凸情况;每4周行双能X线扫描,观察脊柱骨密度(bone mineraldensity,BMD)变化情况;处死大鼠后,测量顶椎旋转度,获取拴系-双足鼠组和PTH干预组大鼠的顶椎及双足鼠组大鼠的第1腰椎后,行显微CT扫描,测量椎体凸凹两侧的BMD和骨微结构参数。结果双足鼠组中无侧凸发生。拴系-双足鼠组和PTH干预组大鼠均出现侧凸畸形,Cobb角在造模后即刻、4周后、8周后随增龄增加(P<0.05)。PTH干预组的Cobb角从造模后第4周开始便小于拴系-双足鼠组,顶椎旋转度也小于拴系-双足鼠组(P<0.05)。PTH干预组的脊柱BMD高于同期的另两组。显微CT显示拴系-双足鼠组的顶椎凹侧的体积骨密度(volumetric BMD,vBMD)、骨体积分数(bone volume fraction,bone volume/total volume,BV/TV)、骨小梁厚度(trabecular thichness,Tb.Th)高于凸侧,骨小梁间隔(trabecular separation,Th.SP)小于凸侧,骨小梁数量(trabecular number,Th.N)在两侧之间的差异无统计学意义。与双足鼠组比较,拴系-双足鼠组的凸侧vBMD及凹侧vBMD、BV/TV、Tb.Th增高,凹侧Tb.Sp缩小。PTH干预后,顶椎凸凹两侧的vBMD和骨微结构参数显著改善,虽两侧仍存在差异,但差异程度较拴系-双足鼠组减小。结论侧凸凹侧逐步提高骨重建水平,强化骨强度,阻碍侧凸的持续性进展。PTH的应用,提前提升骨重建水平,改善BMD和骨微结构,达到了控制侧凸进展的目的,为治疗脊柱侧凸提供了全新思路。

Objective To evaluate the effect of parathyroid hormone in an asymmetric force bipedal rat scoliosis model.Methods 60 SD rats were divided into 3 groups:bipedal rat group,tether-bipedal rat group and parathyroid hormone(PTH) group.Bipedal rat model was made by amputation of the forelimbs and tail.The left inferior angle of scapula to the ipslateral bony pelvis was sutured in tether-bipedal rat group after amputation of the forelimbs and tail.Subcutaneous injection of PTH(20 μg/kg·d) was performed in PTH group.After 8 weeks,the tethering suture was released.Spinal deformity was documented with serial X-ray examinations,and the spinal Bone Mineral Density(BMD) in vivo were measured by serial dual X-ray absorptiometry(DXA) scan at an interval of 4 weeks.After sacrifice,the rotation angle of apical vertebrae was measured and Micro CT was used to analyze the bone micro-architecture.Results All rats in tether-bipedal rat group and PTH group developed scoliosis,and no scoliosis was detected in bipedal rat group.In tether-bipedal rat group and PTH group,the average Cobb angle progressed gradually after the operation and the Cobb angle in PTH group was significantly smaller than the same period tether-bipedal rat.The rotation angle of apical vertebral in PTH group was significantly reduced too.The spinal BMD in vivo increased with age in all groups(P<0.05).Compared to that in bipedal rat group and tether-bipedal rat group,the spinal BMD increased significantly(P<0.05).There was no difference in vBMD,BV/TV、Tb.Th,Tb.N,Tb.Sp between both side of vertebrae in bipedal rat group.The vBMD,BV/TV and Tb.Th on the concave side significantly increased,and Tb.Sp significantly decreased compared with that on the convex side in tether-bipedal rat group.The vBMD,BV/TV and Tb.Th on the concave side and vBMD on the convex side in tether-bipedal rat group significantly increased compared with the bipedal rat group.After the injection of PTH,the vBMD,BV/TV,Tb.Th and Tb.Sp on both sides were significantly improved,and the discrepancy between two sides were significantly reduced,compared to that in tether-bipedal rat group.Conclusion The application of PTH improved the bone remodeling level,BMD and bone microstructures,which can help to prevent the progress of scoliosis.That provided a new sight for the treatment of scoliosis.