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黄芩素抑制白细胞介素-1β诱导的髓核细胞炎症反应,并减轻体内椎间盘退变。

Baicalein Inhibits the IL-1β-Induced Inflammatory Response in Nucleus Pulposus Cells and Attenuates Disc Degeneration In vivo.

机构信息

Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Zhejiang Provincial Key Laboratory of Orthpaedics, Wenzhou, Zhejiang, China.

出版信息

Inflammation. 2019 Jun;42(3):1032-1044. doi: 10.1007/s10753-019-00965-8.

Abstract

Intervertebral disc degeneration (IDD) is widely considered one of the main causes of low back pain, which is a chronic progressive disease closely related to inflammation and degeneration of nucleus pulposus (NP) cells. Baicalein is a natural bioactive compound with anti-inflammatory effects in different diseases, including inhibition of the inflammatory response in chondrocytes, whose morphology and avascular supply are similar to those of NP cells. Therefore, we hypothesized that baicalein may have a therapeutic effect on IDD by suppressing the inflammatory response. In vitro, NP cells were pretreated with baicalein for 2 h and then incubated with IL-1β for 24 h. We found that baicalein not only inhibited the overexpression of inflammatory cytokine production, including NO, PGE2, TNF-α, and IL-6, but also suppressed the expression of COX-2 and iNOS. The IL-1β-induced overexpression of MMP13 and ADAMTS5 and degradation of aggrecan and type II collagen were reversed by baicalein in a dose-dependent manner. Mechanistically, we found that baicalein suppressed the IL-1β-induced activation of the NF-κB and MAPK pathways. Moreover, an in vivo study demonstrated that baicalein treatment could ameliorate IDD in a puncture-induced rat model. Thus, baicalein has great value as a potential therapeutic agent for IDD.

摘要

椎间盘退变(IDD)被广泛认为是腰痛的主要原因之一,腰痛是一种慢性进行性疾病,与核髓细胞的炎症和退变密切相关。黄芩素是一种具有抗炎作用的天然生物活性化合物,在包括软骨细胞炎症反应抑制在内的多种疾病中都有作用,软骨细胞的形态和无血管供应与 NP 细胞相似。因此,我们假设黄芩素通过抑制炎症反应可能对 IDD 有治疗作用。在体外,NP 细胞用黄芩素预处理 2 h 后,再用 IL-1β孵育 24 h。我们发现黄芩素不仅抑制了炎症细胞因子(包括 NO、PGE2、TNF-α 和 IL-6)的过度表达,还抑制了 COX-2 和 iNOS 的表达。黄芩素以剂量依赖性方式逆转了 IL-1β诱导的 MMP13 和 ADAMTS5 的过度表达以及聚集蛋白聚糖和 II 型胶原的降解。在机制上,我们发现黄芩素抑制了 IL-1β诱导的 NF-κB 和 MAPK 通路的激活。此外,一项体内研究表明,黄芩素治疗可改善穿刺诱导的大鼠 IDD 模型。因此,黄芩素作为一种潜在的 IDD 治疗药物具有很大的价值。

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