Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Cell Death Dis. 2018 Jan 24;9(2):98. doi: 10.1038/s41419-017-0151-z.
Intervertebral disc degeneration (IVDD) is one of the key predisposing factors for low back pain. Although the exact mechanism remains unclear, inflammatory response and nucleus pulposus (NP) apoptosis are known to play important roles in this process. Prolactin protects against inflammation-associated chondrocyte apoptosis in arthritis. Based on prior studies, we hypothesized that prolactin might have therapeutic effects on IVDD by inhibiting the apoptosis of degenerative human disc NP cells. An experimental model of IVDD was established in 3-month-old Sprague-Dawley rats by submitting them to percutaneous disc puncture with a 20-gauge needle on levels 7-8 and 8-9 of the coccygeal vertebrae. Then the rats were injected with 20 or 200 ng prolactin on a weekly basis. Radiologic and histologic analyses were performed on days 4, 7, 14, and 28. The expression of prolactin and its receptor was analyzed in human tissue obtained from symptomatic patients undergoing microencoscopy discectomy, or from scoliosis patients undergoing deformity correction surgery. The results showed that intradiscal injection of prolactin maintained disc height and the mean signal intensity of the punctured disc. Histological analysis indicated that prolactin treatment significantly retained the complete structure of the NP and annulus fibrosus compared with the vehicle group. In addition, more collagen II, but fewer collagen I-containing tissues were detected in the prolactin treatment groups compared to the vehicle group. Moreover, low levels of tumor necrosis factor-α, interleukin-1β, cleaved-caspase 3, and TUNEL staining were observed in the prolactin treatment groups. We also demonstrated that prolactin impaired puncture-induced inflammation and cell apoptosis by downregulating activation of the NF-κB pathway. The degenerated NP tissues from patients had decreased expression of prolactin and its receptor, whereas expression was increased in the NP tissues removed from scoliosis patients. These results suggest that prolactin may be a novel therapeutic target for the treatment of IVDD.
椎间盘退变（IVDD）是腰痛的主要诱发因素之一。尽管确切的机制尚不清楚，但已知炎症反应和髓核（NP）细胞凋亡在这一过程中起重要作用。催乳素可防止关节炎中炎症相关软骨细胞凋亡。基于先前的研究，我们假设催乳素可能通过抑制退变人椎间盘 NP 细胞的凋亡对 IVDD 具有治疗作用。通过在尾骨椎骨 7-8 和 8-9 水平用 20 号针进行经皮椎间盘穿刺，在 3 月龄 Sprague-Dawley 大鼠中建立 IVDD 实验模型。然后每周向大鼠注射 20 或 200ng 催乳素。在第 4、7、14 和 28 天进行放射学和组织学分析。分析了来自接受微创椎间盘切除术的症状患者或接受脊柱侧凸畸形矫正手术的患者的人组织中催乳素及其受体的表达。结果表明，催乳素的椎间盘内注射维持了椎间盘的高度和穿刺椎间盘的平均信号强度。组织学分析表明，与载体组相比，催乳素治疗组明显保留了 NP 和纤维环的完整结构。此外，与载体组相比，催乳素治疗组检测到更多的 II 型胶原蛋白，但含 I 型胶原蛋白的组织较少。此外，催乳素治疗组肿瘤坏死因子-α、白细胞介素-1β、裂解 caspase 3 和 TUNEL 染色的水平较低。我们还表明，催乳素通过下调 NF-κB 通路的激活来损害穿刺引起的炎症和细胞凋亡。来自患者的退变 NP 组织中催乳素及其受体的表达减少，而在脊柱侧凸患者中切除的 NP 组织中表达增加。这些结果表明，催乳素可能是治疗 IVDD 的一种新的治疗靶点。
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