Wu Yifan, Wang Zhanghong, Lin Zeng, Fu Xin, Zhan Jingdi, Yu Kehe
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Front Pharmacol. 2020 Jun 3;11:682. doi: 10.3389/fphar.2020.00682. eCollection 2020.
Osteoarthritis (OA) is a degenerative disease found in middle-aged and elderly people, which seriously affects their quality of life. The anti-inflammatory and anti-apoptosis pharmacological effects of salvianolic acid A (SAA) have been shown in many studies. In this study, we intended to explore the anti-inflammatory and anti-apoptotic effects of SAA in OA. We evaluated the expression of pro-inflammatory mediators and cartilage matrix catabolic enzymes in chondrocytes by ELISA, Griess reaction, immunofluorescence, and Western blot, which includes nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), MMPs (MMP-3, MMP-13), and ADAMTS-5. Bax, Bcl-2, and cleaved caspase-3 were also measured by Western blot methods. The results of this experiment showed that SAA not only inhibited the production of inflammatory mediators induced by IL-1β and the loss of cartilage matrix but also reduced the apoptosis of mouse chondrocytes induced by IL-1β. According to the results of immunofluorescence and Western blot, SAA inhibited the activation of the NF-κB pathway and MAPK pathway. The results of these experiments revealed for the first time that SAA down-regulated the production of inflammatory mediators and inhibited the apoptosis of mouse chondrocytes and the degradation of extracellular matrix (ECM), which may be attributed to the inhibition of the activation of NF-κB and MAPK signaling pathways. In the experiments, 45 mice were randomly divided among three groups (the sham group, OA group, and OA + SAA group). The results of animal experiments showed that SAA treatment for eight consecutive weeks inhibited further deterioration of OA. These results demonstrate that SAA plays an active therapeutic role in the development of OA.
骨关节炎(OA)是一种在中老年人中发现的退行性疾病,严重影响他们的生活质量。许多研究表明丹酚酸A(SAA)具有抗炎和抗凋亡的药理作用。在本研究中,我们旨在探讨SAA在OA中的抗炎和抗凋亡作用。我们通过ELISA、Griess反应、免疫荧光和蛋白质印迹法评估软骨细胞中促炎介质和软骨基质分解酶的表达,这些介质和酶包括一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、前列腺素E2(PGE2)、诱导型一氧化氮合酶(iNOS)、环氧化酶-2(COX-2)、基质金属蛋白酶(MMP-3、MMP-13)和含血小板反应蛋白基序的解聚蛋白样金属蛋白酶-5(ADAMTS-5)。还通过蛋白质印迹法检测了Bax、Bcl-2和裂解的半胱天冬酶-3。本实验结果表明,SAA不仅抑制IL-1β诱导的炎症介质产生和软骨基质丢失,还减少了IL-1β诱导的小鼠软骨细胞凋亡。根据免疫荧光和蛋白质印迹结果,SAA抑制了NF-κB通路和丝裂原活化蛋白激酶(MAPK)通路的激活。这些实验结果首次表明,SAA下调炎症介质的产生,抑制小鼠软骨细胞凋亡和细胞外基质(ECM)降解,这可能归因于对NF-κB和MAPK信号通路激活的抑制。在实验中,45只小鼠被随机分为三组(假手术组、OA组和OA + SAA组)。动物实验结果表明,连续八周给予SAA治疗可抑制OA的进一步恶化。这些结果表明,SAA在OA的发展中发挥着积极的治疗作用。