Department of Orthopedic Surgery, Hebei Medical University, 361 Zhongshan E Rd, Shijiazhuang, Hebei, 050000, People's Republic of China.
Medical Research Center, North China University of Science and Technology, Tangshan, People's Republic of China.
J Orthop Surg Res. 2021 Jun 9;16(1):368. doi: 10.1186/s13018-021-02504-4.
Adjacent segmental intervertebral disk degeneration (ASDD) is a major complication secondary to lumbar fusion. Although ASSD pathogenesis remains unclear, the primary cause of intervertebral disk degeneration (IVDD) development is apoptosis of nucleus pulposus (NP). Raloxifene (RAL) could delay ASDD by inhibiting NP apoptosis.
An ASDD rat model was established by ovariectomy (OVX) and posterolateral spinal fusion (PLF) on levels 4-5 of the lumbar vertebrae. Rats in the treatment groups were administered 1 mg/kg/d RAL by gavage for 12 weeks, following which, all animals were euthanized. Lumbar fusion, apoptosis, ASDD, and vertebrae micro-architecture were evaluated.
RAL maintained intervertebral disk height (DHI), delayed vertebral osteoporosis, reduced histological score, and inhibited apoptosis. The OVX+PLF+RAL group revealed upregulated expression of aggrecan and B-cell lymphoma-2 (bcl2), as well as significantly downregulated expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), metalloproteinase-13 (MMP-13), caspase-3, BCL2-associated X (bax), and transferase dUTP nick end labeling (TUNEL) staining. Micro-computed tomography (Micro-CT) analysis revealed higher bone volume fraction (BV/TV), bone mineral density (BMD), and trabecular number (Tb.N), and lower trabecular separation (Tb.Sp) in OVX+PLF+RAL group than in the OVX+PLF group.
RAL can postpone ASDD development in OVX rats through inhibiting extracellular matrix metabolic imbalance, NP cell apoptosis, and vertebral osteoporosis. These findings showed RAL as a potential therapeutic target for ASDD.
邻近节段椎间盘退变（ASDD）是腰椎融合术后的主要并发症。虽然 ASDD 的发病机制尚不清楚，但椎间盘退变（IVDD）发展的主要原因是髓核（NP）细胞凋亡。雷洛昔芬（RAL）通过抑制 NP 细胞凋亡可延缓 ASDD。
通过卵巢切除术（OVX）和后路脊柱融合术（PLF）在腰椎 4-5 节段建立 ASDD 大鼠模型。治疗组大鼠灌胃给予 1mg/kg/d RAL 共 12 周，然后处死所有动物。评估腰椎融合、凋亡、ASDD 和椎体微结构。
RAL 维持椎间盘高度（DHI），延缓椎体骨质疏松，降低组织学评分，并抑制细胞凋亡。OVX+PLF+RAL 组聚集蛋白和 B 细胞淋巴瘤-2（bcl2）表达上调，而解整合素金属蛋白酶与凝血酶敏感蛋白 4（ADAMTS-4）、基质金属蛋白酶-13（MMP-13）、半胱天冬酶-3、Bcl2 相关 X（bax）和转移酶 dUTP 缺口末端标记（TUNEL）染色表达下调。微计算机断层扫描（Micro-CT）分析显示 OVX+PLF+RAL 组的骨体积分数（BV/TV）、骨密度（BMD）和小梁数（Tb.N）较高，而骨小梁分离度（Tb.Sp）较低。
RAL 可通过抑制细胞外基质代谢失衡、NP 细胞凋亡和椎体骨质疏松来延缓 OVX 大鼠的 ASDD 发展。这些发现表明 RAL 可能是 ASDD 的潜在治疗靶点。
