Zhu Bin, Wang Xuejian, Teng Jiawen
Department of Orthopedics, Baodi Clinical College of Tianjin Medical University Tianjin 301800 China.
Department of Orthopedics, Affiliated Hospital of Shandong Traditional Chinese Medicine University No. 16369 Jingshi Road, Shizhong District Jinan Shandong 250014 PR China
RSC Adv. 2018 Oct 29;8(64):36422-36429. doi: 10.1039/c8ra02418a. eCollection 2018 Oct 26.
Osteoarthritis (OA) is the most common joint disease among late middle-aged or elderly people. The pathological process of OA mainly involves the degeneration of cartilage tissue and deficiency of joint function. Salvianolic acid B (Sal B) is the main active ingredient of Bge, which possesses anti-inflammatory, anti apoptotic and other pharmacological activities. In this study, primary chondrocytes were cultured to investigate the effects of Sal B on the inflammatory response and apoptosis of OA induced by IL-1β, and to explore the possible mechanism. First, we determined the cytotoxicity of Sal B; the results showed that the cell activity of chondrocytes was not influenced by Sal B when the concentration was below 150 μM. Moreover, Sal B (40 and 80 μM) suppressed the expression of iNOS in OA chondrocytes induced by IL-1β, and restrained the secretion of NO, IL-6, IL-17 and TNF-α in chondrocytes obviously. Sal B (40, 80 μM) significantly alleviated the inhibitory effect of cell activity stimulated by IL-1β and up-regulated the expression of Col II and reduced the expression of Col X. Besides, Sal B down-regulated the expression level of Bax and promoted the expression of Bcl-2, showed a significant effect on promoting proliferation and inhibiting cell apoptosis. In addition, we found that IL-1β significantly reduced the ratio of p-PI3K/PI3K, p-Akt/Akt induced the nuclear translocation of AKT and inhibited the activation of the PI3K/Akt signaling pathway. Finally, the PI3K inhibitor, LY-294002, was added in IL-1β-induced chondrocytes. The results suggest that Sal B ameliorates IL-1β induced inflammation and suppresses apoptosis in OA by activating the PI3K/Akt signaling pathway. Our study reveals the mechanism of Sal B acts on OA and may provide a basis for the treatment of OA with Sal B.
骨关节炎（OA）是中老年人群中最常见的关节疾病。OA的病理过程主要涉及软骨组织退变和关节功能缺失。丹酚酸B（Sal B）是丹参的主要活性成分，具有抗炎、抗凋亡等药理活性。本研究通过培养原代软骨细胞，探讨Sal B对白细胞介素-1β（IL-1β）诱导的OA炎症反应和细胞凋亡的影响，并探究其可能机制。首先，我们测定了Sal B的细胞毒性；结果显示，当浓度低于150μM时，Sal B对软骨细胞的活性没有影响。此外，Sal B（40和80μM）抑制了IL-1β诱导的OA软骨细胞中诱导型一氧化氮合酶（iNOS）的表达，并显著抑制了软骨细胞中一氧化氮（NO）、白细胞介素-6（IL-6）、白细胞介素-17（IL-17）和肿瘤坏死因子-α（TNF-α）的分泌。Sal B（40、80μM）显著减轻了IL-1β对细胞活性的抑制作用，上调了Ⅱ型胶原（Col II）的表达，降低了Ⅹ型胶原（Col X）的表达。此外，Sal B下调了促凋亡蛋白Bax的表达水平，促进了抗凋亡蛋白Bcl-2的表达，对促进细胞增殖和抑制细胞凋亡具有显著作用。另外，我们发现IL-1β显著降低了磷酸化磷脂酰肌醇-3激酶（p-PI3K）/PI3K、磷酸化蛋白激酶B（p-Akt）/Akt的比值，诱导Akt核转位并抑制PI3K/Akt信号通路的激活。最后，在IL-1β诱导的软骨细胞中加入PI3K抑制剂LY-294002。结果表明，Sal B通过激活PI3K/Akt信号通路改善IL-1β诱导的OA炎症并抑制细胞凋亡。我们的研究揭示了Sal B作用于OA的机制，可能为Sal B治疗OA提供依据。
