| 摘要: |
| 目的 探讨奈立膦酸钠对卵巢切除大鼠骨质疏松相关腰椎间盘退变的影响。方法 3个月龄雌性SD大鼠随机分为3组(n=10):假手术(Sham)组;卵巢切除+奈立膦酸钠(OVx+N)组,皮下注射奈立膦酸钠(15 μg/kg)每周2次,共6个月;卵巢切除+安慰剂(OVx+PBO)组,皮下注射相同剂量安慰剂。6个月后处死大鼠,进行骨密度(BMD)测定、骨组织形态计量学检测以及生物力学性能测试;通过组织学分析和评分确定椎间盘退化进程,并测量椎间隙高度和软骨终板厚度;采用蛋白质印迹法和real-time RT-PCR法测定卵巢切除大鼠椎间盘组织Ⅰ型胶原(COL-Ⅰ)、Ⅱ型胶原(COL-Ⅱ)、基质金属蛋白酶1(MMP-1)、基质金属蛋白酶3(MMP-3)及基质金属蛋白酶13(MMP-13)的表达水平。结果 与OVx+PBO组相比,OVx+N组椎间盘骨密度、骨组织形态计量学指标以及生物学强度较好;组织学评估结果表明,OVx+N组大鼠椎间盘高度低于Sham组,软骨终板厚度高于Sham组,但差异无统计学意义,提示奈立膦酸钠有利于维持椎间盘高度,延缓软骨终板钙化程度;OVx+N组的组织学评分低于OVx+PBO组(P<0.05),提示奈立膦酸钠可有效延迟椎间盘退化进程。分子生物学结果显示:与OVx+PBO组相比,OVx+N组椎间盘组织COL-Ⅰ和COL-Ⅱ水平升高(P<0.05),且MMP-1、MMP-3及MMP-13在蛋白及基因表达水平均下降(P<0.05)。结论 奈立膦酸钠能延迟卵巢切除大鼠腰椎间盘退化进程,可能与其保持腰椎结构完整性,促进COL-Ⅰ和COL-Ⅱ表达及抑制MMP-1、MMP-3、MMP-13表达有关。 |
| 关键词: 奈立膦酸钠 卵巢切除术 腰椎 椎间盘 退变 |
| DOI：10.3724/SP.J.1008.2015.00936 |
| 投稿时间：2015-01-20修订日期：2015-05-22 |
| 基金项目: |
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| Effect of neridronate on degeneration of lumbar disc in ovariectomized rats |
| WU Zhao,WANG Yuan,WANG Hai-bo,SHI Jian-gang* |
(Department of Orthopedics, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the effect of neridronate on osteoporosis-associated degeneration of lumbar disc in ovariectomized rats. Methods Totally 30 female SD rats, aged 3 months old, were divided into three groups randomly: Sham group, OVx (ovariectomy) +N (neridronate) group (receiving a subcutaneous injection of 15 μg/kg neridronate twice a week for 6 months), and OVx + PBO (placebo) group (receiving the same dosage of placebo). The rats were sacrificed and the bone mineral density (BMD), bone histomorphometry and biomechanical properties were measured 6 months later. The histological analysis and score were used to determine the process of lumbar disc degeneration, and the disc height index (DHI) and thickness of cartilage endplate (TCE) were also measured. The protein and mRNA expression levels of collagen type Ⅰ (COL-Ⅰ), collagen type Ⅱ (COL-Ⅱ), matrix metalloproteinase-1(MMP-1), matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13) in the lumbar disc of ovariectomized rats were detected by Western blotting analysis and real-time RT-PCR, respectively. Results The BMD, bone histomorphometry and biomechanical properties were better in the OVx+N group compared with OVx+PBO group. Histological evaluation showed that the DHI of rats in the OVx+N group was shorter than that in the Sham group, and the TCE of rats in the OVx+N group was higher than that in the Sham group, but showing no significant difference, which indicated that neridronate could effectively maintain the DHI and delay the calcification of the cartilage endplate. The histological score of the OVx+N group was significantly lower than that of the OVx+PBO group (P<0.05), suggesting neridronate could delay the degeneration of lumbar disc. We also found that, compared with the OVx+PBO, the protein and mRNA expression levels of COL-Ⅰ and COL-Ⅱ in the OVx+N group were significantly higher and those of MMP-1, MMP-3 and MMP-13 were significantly reduced (P<0.05). Conclusion Neridronate can delay the process of lumbar disc degeneration in ovariectomized rats, which may be related to maintaining the integrity of lumbar, promoting COL-Ⅰ and COL-Ⅱ expression and suppressing MMP-1, MMP-3 and MMP-13 expression. |
| Key words: neridronate ovariectomy lumbar vertebrae intervertebral disc degeneration |
