体内和体外研究表明，通过减轻炎症和氧化应激，CB2 介导的椎间盘退变的衰减。
CB2-mediated attenuation of nucleus pulposus degeneration via the amelioration of inflammation and oxidative stress in vivo and in vitro.
机构信息
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188, Shi Zi Road, 215006, Suzhou, China.
Department of Orthopaedics, Nanjing First Hospital, Nanjing Medical University, 210000, Nanjing, China.
出版信息
Mol Med. 2021 Aug 19;27(1):92. doi: 10.1186/s10020-021-00351-x.
BACKGROUND
Nucleus pulposus cell (NPC) degeneration is widely accepted as one of the major causes of intervertebral disc (IVD) degeneration (IVDD). The pathogenesis of IVDD is complex and consists of inflammation, oxidative stress, and the loss of extracellular matrix (ECM). Cannabinoid type 2 receptor (CB2) has been shown to be involved in the pathological mechanism of a variety of diseases due to its anti-inflammatory effects and antioxidative stress capacity.
METHOD
In Vitro, HO was used to induce degeneration of nucleus pulposus cells, mRNA and protein expression level was determined by RT-PCR and Western Blot, and Immunocytochemical staining were used to detect expression of collagen II, aggrecan, MMP3/13, superoxide dismutase 2 (SOD2) and inducible nitric oxide synthase (iNOS). In vivo, the potential therapeutic effect of CB2 was detected in the rat acupuncture model.
RESULT
In vitro, we found that the CB2 agonist (JWH133) treatment reduced the oxidative stress level in NPCs induced by hydrogen peroxide (HO) treatment. Furthermore, the expression of inflammatory cytokines was also decreased by JWH133 treatment. We found that collagen II and aggrecan expression was preserved, whereas matrix metalloproteinase levels were reduced. In vivo, we established a rat model by needle puncture. Imaging assessment revealed that the disc height index (DHI) and morphology of IVD were significantly improved, and the disc degeneration process was delayed by treatment of JWH133. Furthermore, immunohistochemical (IHC) staining revealed that JWH133 could inhibit the degradation of collagen II and decrease the expression of MMP3.
CONCLUSIONS
The experiment indicates the oxidative stress and inflammatory response of rat NPCs induced by HO could be inhibited by activating CB2. This study reveals that CB2 activation can effectively delay the development of IVDD, providing an effective therapeutic target for IVDD.
背景
髓核细胞（NPC）退变被广泛认为是椎间盘退变（IVDD）的主要原因之一。IVDD 的发病机制复杂，包括炎症、氧化应激和细胞外基质（ECM）的丢失。由于大麻素 2 型受体（CB2）具有抗炎作用和抗氧化应激能力，因此已证明其参与了多种疾病的病理机制。
方法
在体外，使用 HO 诱导 NPC 退变，通过 RT-PCR 和 Western blot 测定 mRNA 和蛋白表达水平，并用免疫细胞化学染色检测 II 型胶原、聚集蛋白聚糖、MMP3/13、超氧化物歧化酶 2（SOD2）和诱导型一氧化氮合酶（iNOS）的表达。在体内，在大鼠针刺模型中检测 CB2 的潜在治疗效果。
结果
在体外，我们发现 CB2 激动剂（JWH133）处理可降低过氧化氢（HO）处理诱导的 NPC 氧化应激水平。此外，JWH133 处理还降低了炎症细胞因子的表达。我们发现胶原 II 和聚集蛋白聚糖的表达得到保留，而基质金属蛋白酶水平降低。在体内，我们通过针刺建立了大鼠模型。影像学评估显示，椎间盘高度指数（DHI）和 IVD 形态得到显著改善，JWH133 治疗可延迟椎间盘退变过程。此外，免疫组织化学（IHC）染色显示，JWH133 可抑制胶原 II 的降解并降低 MMP3 的表达。
结论
实验表明，HO 诱导的大鼠 NPC 的氧化应激和炎症反应可通过激活 CB2 得到抑制。本研究表明，CB2 激活可有效延缓 IVDD 的发展，为 IVDD 提供了有效的治疗靶点。
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