去势大鼠体内TAZ转染对股骨颈骨密度和力学的影响

Effect of TAZ transfection in vivo on bone mineral density and mechanical characteristics of femoral neck in ovariecto⁃ mized rats

摘要:

[目的] 研究慢病毒 TAZ 基因转染对去势骨质疏松股骨大鼠骨密度和生物力学特性的影响。[方法] 6 个月龄雌性 SD 大鼠 90 只随机分为两组，25 只行假手术，65 只行双侧卵巢切除（ovariectomy, OVX），3 周后各 6 只动物检测骨密度和股骨力学特性。其余 OVX 动物再分为 3 组，于股骨颈钻孔，TAZ 组向髓腔内注射慢病毒 TAZ 制剂，Cherry 组注入慢病毒 Cherry 制剂，钻孔组不注射任何药物。此外，原假手术组动物为正常对照。再行股骨颈骨密度和股骨颈骨生物力学检测。[结果]OVX 术后 3 个月，假手术组大鼠股骨颈骨密度 [(0.217±0.11) g/cm² vs (0.158±0.03) g/cm², P＜0.001]、股骨颈最大载荷 [(108.6±6.1) N vs (83.3±5.8) N, P＜0.001] 和刚度 [(338.8±11.1) N/mm vs (226.4±12.9) N/mm, P＜0.001] 均显著高于 OVX 组。体内转染后第 1、2、3 个月，四组股骨颈骨密度、股骨最大载荷和刚度均由高至低依次为：假手术组＞TAZ 组＞Cherry 组＞钻孔组，整体差异均有统计学意义（P＜0.05）。两两比较，TAZ 组股骨颈骨密度、股骨最大载荷和刚度均显著低于假手术组（P＜0.05）；而 TAZ 组骨密度、最大载荷均显著高于 Cherry 组（P＜0.05），TAZ 组刚度高于 Cherry 组，但差异无统计学意义（P＞0.05）；Cherry 组与钻孔组之间骨密度、最大载荷和刚度的差异均无统计学意义 （P＞0.05）。随转染后时间推移，TAZ 组的股骨颈骨密度、股骨最大载荷和刚度均显著增加（P＜0.05）；Cherry 组股骨颈骨密度显著下降（P＜0.05）、而股骨最大载荷和刚度无显著变化（P＞0.05）；钻孔组股骨颈骨密度呈沟槽样显著变化（P＜0.05），而股骨最大载荷和刚度均显著减少（P＜0.05）。[结论]慢病毒介导的 TAZ 基因转染至 OVX 后骨质疏松大鼠股骨颈，可以显著增加骨质疏松大鼠股骨颈的骨密度，增强股骨颈的骨生物力学强度。

Abstract:

[Objective] To investigate the effects of lentivirus TAZ gene transfection on bone mineral density (BMD) and biomechanical characteristics of the femur neck in the ovariectomized rats. [Methods] A total of 90 6-month-old female SD rats were randomly divided in- to two groups, 25 underwent sham operation (SO) and 65 underwent bilateral ovariectomy (OVX). The BMD and femur mechanical proper- ties were tested in 6 animals in each group 3 weeks after OVX, while the remaining OVX animals were furtherly divided into 3 groups. After femoral neck was drilled, the TAZ group was injected with lentivirus TAZ, the Cherry group was injected with lentivirus Cherry, while the drilled group was not injected with any drug. In addition, the remaining animals in the SO group were used as normal controls. The BMD and biomechanics of the femoral neck were assessed again. [Results] The SO group had significantly higher BMD [(0.217±0.11) g/cm² vs (0.158±0.03) g/cm², P＜0.001], maximum load of the femoral neck [(108.6±6.1) N vs (83.3±5.8) N, P＜0.001] and stiffness [(338.8±11.1) N/ mm vs (226.4±12.9) N/mm , P＜0.001] than the OVX group 3 weeks after OVX. At 1, 2 and 3 months after in vivo transfection, the BMD, maximum load and stiffness of femoral neck in the four groups were all ranked from high to low as SO group＞TAZ＞Cherry Group＞ drilled group, with statistically significant overall differences among them (P＞0.05). Regarding to pairwise comparison, the TAZ group was signifi- cantly lower in terms of BMD, maximum load and stiffness of femoral neck than the SO group (P＜0.05), while significantly higher in BMD and maximum loading than Cherry group (P＜0.05) regardless of that the difference was not statistically significant in stiffness between them (P＞0.05). However, there were no significant differences in BMD, maximum load and stiffness between Cherry group and drilled group (P＜ 0.05). As time went after in vivo transfection, the TAZ group got significant increase of BMD, maximum load and stiffness (P＜0.05), where- as the Cherry group had significant decrease in BMD (P＜0.05), and no significant changes in maximum load and stiffness of femur (P＞0.05). The drilled group was of significant groove-like changes in BMD (P＜0.05), while significantly decline in the maximum load and stiff- ness of femur neck (P＜0.05). [Conclusion] The lentivirus-mediated TAZ gene transfection into OVX rats does significantly increase bone mineral density and enhance bone biomechanical strength.