Effects of Artesunate on chondrocyte proliferation, apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway in rat models with rheumatoid arthritis (Retracted article. See vol. 162, 2023)
Effects of Artesunate on chondrocyte proliferation, apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway in rat models with rheumatoid arthritis (Retracted article. See vol. 162, 2023)
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DOI：
10.1016/j.biopha.2018.03.142
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发表时间：
2018-06-01
影响因子：
7.5
通讯作者：
Qiu, Hai-Yan
中科院分区：
文献类型：
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作者：
Feng, Fa-Bo;Qiu, Hai-Yan
背景：类风湿性关节炎(RA)是一种长期的自身免疫性疾病，主要导致关节温暖、肿胀和疼痛。本研究通过PI3K/AKT/mTOR信号通路探讨青蒿琥酯(Art)对类风湿关节炎(RA)软骨细胞增殖、凋亡和自噬的潜在治疗作用。免疫组织化学方法检测PI3K、AKT、mTOR蛋白阳性表达率。RA软骨细胞最初被随机分为五组。RT-qPCR检测PI3K、AKT、mTOR、Bcl2、Bclxl、Lc3-I、Lc3-II和Becline-1的mRNA表达。免疫印迹法检测p-PI3K、p-AKT、p-mTOR、Bcl2、Bclxl、Bax、Lc3-I、Lc3-II和Becline-1的蛋白表达。分离培养RA大鼠和正常大鼠的软骨细胞。用CCK-8比色法、流式细胞仪和透射电子显微镜检测软骨细胞的增殖、凋亡、细胞周期和自噬。结果：青蒿琥酯可减轻RA大鼠的炎症反应，且不产生任何形式的肝毒性。此外，青蒿琥酯还可降低PI3K、AKT、mTOR、p-PI3K、p-AKT、p-mTOR、Bcl2和Bclxl的表达，增加Bax、LC3II/LC3I和Becline-1蛋白的表达。青蒿琥酯通过抑制PI3K/AKT/mTOR信号通路抑制软骨细胞增殖，促进细胞凋亡和自噬。结论：青蒿琥酯通过PI3K/AKT/mTOR信号通路抑制RA大鼠软骨细胞增殖，促进细胞凋亡和自噬。
Background: Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily results in warm, swollen, and painful joints. In this study, we investigate the potentially therapeutic role of artesunate (Art) on chondrocyte proliferation, apoptosis and autophagy in rheumatoid arthritis (RA) via the PI3K/AKT/mTOR signaling pathway.Methods: Rat model of RA was successfully established through subcutaneous injection of emulsion. Positive protein expression rates of PI3K, AKT and mTOR were determined by immunohistochemistry. RA chondrocytes were initially randomized into five different groups. The mRNA expressions of PI3K, AKT, mTOR, Bcl-2, Bcl-xl, LC3-I,LC3-II and Becline-1 were measured by RT-qPCR. Protein expressions of p-PI3K, p-AKT, p-mTOR, Bcl-2, Bcl-xl,Bax, LC3-I, LC3-II and Becline-1 were determined using western blotting. The chondrocytes of rats with RA and normal rats were isolated and cultured in vitro. Chondrocyte proliferation, apoptosis, cell cycle and autophagy were all determined by CCK-8 assay, flow cytometry and transmission electron microscope (TEM).Results: Artesunate alleviated the inflammation and did not produce any form of hepatotoxicity in rats with RA. In addition, Artesunate decreased expressions of PI3K, AKT, mTOR, p-PI3K, p-AKT, p-mTOR Bcl-2 and Bcl-xl and increased Bax, LC3II/LC3I and Becline-1 protein expression. Artesunate also inhibited chondrocyte proliferation and accelerates cell apoptosis and autophagy via suppression of the PI3K/AKT/mTOR signaling pathway.Conclusion: Our study demonstrates that Art inhibits chondrocyte proliferation and accelerates apoptosis and autophagy in RA rats through the PI3K/AKT/mTOR signaling pathway.