■椎间盘退变(IDD)是脊柱退行性疾病的发病机理;然而,其确切的分子机制尚不清楚。
■探讨机械压力(MP)诱导IDD的分子机制,探讨瑞舒伐他汀(RSV)抑制MP诱导IDD的作用和机制。
■体外培养SD大鼠髓核细胞(NPCs),并使用MP构建NPCs的凋亡模型。增殖活性,活性氧含量,凋亡,并检测各组NPC的伤口愈合情况,分别。通过qPCR和WesternBlot技术检测相关蛋白的表达。18只SD大鼠随机分为对照组,压力和RSV组。Elisa,qPCR,采用WesternBlot和免疫组化染色技术检测各组椎间盘内相关蛋白含量的变化。HE染色和改良藏红花O和固绿染色试剂盒用于评估各组的IDD。
■1.0MPaMP处理24h后可显著诱导NPCs凋亡。MP可显著抑制NPCs的增殖活性和创面愈合能力,RSV预处理能显著激活Nrf2/HO-1信号通路,逆转MP对细胞的损伤;当抑制Nrf2/HO-1信号通路激活时,RSV的保护作用被逆转。体内MP能显著增加IVD内炎症因子的含量,促进细胞外基质的降解,导致IDD。当采用RSV干预时,能显著激活Nrf2/HO-1信号通路,改善上述结果。
■RSV可能通过激活Nrf2/HO-1信号通路抑制MP诱导的NPCs损伤和IDD。
UNASSIGNED: Intervertebral disc degeneration (IDD) underlies the pathogenesis of degenerative diseases of the spine; however, its exact molecular mechanism is unclear.
UNASSIGNED: To explore the molecular mechanism of mechanical pressure (MP)-induced IDD and to assess the role and mechanism of Rosuvastatin (RSV) inhibits MP-induced IDD.
UNASSIGNED: SD rat nucleus pulposus cells (NPCs) were cultured in vitro and an apoptosis model of NPCs was constructed using MP. Proliferative activity, reactive oxygen species content, apoptosis, and wound healing were detected in each group of NPCs, respectively. The expression of relevant proteins was detected by qPCR and Western Blot techniques. 18 SD rats were randomly divided into control, pressure and RSV groups. Elisa, qPCR, Western Blot and immunohistochemical staining techniques were used to detect changes in the content of related proteins in the intervertebral discs of each group. HE staining and Modified Saffron-O and Fast Green Stain Kit were used to assess IDD in each group.
UNASSIGNED: MP treatment at 1.0 MPa could significantly induce apoptosis of NPCs after 24 h. MP could significantly inhibit the proliferative activity and wound healing ability of NPCs, and increase the intracellular reactive oxygen species content and apoptosis rate; pretreatment with RSV could significantly activate the Nrf2/HO-1 signaling pathway and reverse the cellular damage caused by MP; when inhibit the Nrf2/HO-1 signaling pathway activation, the protective effect of RSV was reversed. In vivo MP could significantly increase the content of inflammatory factors within the IVD and promote the degradation of extracellular matrix, leading to IDD. When the intervention of RSV was employed, it could significantly activate the Nrf2/HO-1 signaling pathway and improve the above results.
UNASSIGNED: RSV may inhibit MP-induced NPCs damage and IDD by activating the Nrf2/HO-1 signaling pathway.