Abstract：
Mastitis, one of the most significant problems in women, is commonly caused by pathogens, especially Staphylococcus aureus (S.aureus). Schisandrin B (SCB), the main abundant derivatives from Schisandra chinensis, has been proven to have the ability to inhibiting inflammation and bacteria. However, few relevant researches systematically illustrate the role SCB in the treatment of mastitis. The aim of the present study is to demonstrate the mechanism that SCB functions in reducing pathological injury to the mammary gland in treating S.aureus-induced mastitis. H&E staining was used to identify pathological changes and injuries in mastitis. The levels of cytokines associated with inflammation were detected by ELISA. Key signals relevant to ferroptosis and Nrf2 signaling pathway were tested by western blot analysis and iron assay kit. Compared with the control group, inflammation-associated factors, such as IL-1β, TNF-α, MPO activity, increased significantly in S. aureus-treated mice. However, these changes were inhibited by SCB. Ferroptosis-associated factors Fe2+ and MDA increased significantly, and GSH, GPX4 and ferritin expression decreased markedly in S. aureus-treated mice. SCB treatment could attenuate S.aureus-induced ferroptosis. Furthermore, SCB increase SIRT1 and SLC7A11 expression and down-regulated p53 expression and NF-κB activation. In conclusion, SCB alleviates S.aureus-induced mastitis via up-regulating SIRT1/p53/SLC7A11 signaling pathway, attenuating the activation of inflammation-associated cytokines and ferroptosis in the mammary gland tissues.
摘要：
乳腺炎,女性最重要的问题之一，通常是由病原体引起的，尤其是金黄色葡萄球菌(S.金黄色葡萄球菌）。五味子B（SCB），五味子主要丰富的衍生物，已被证明具有抑制炎症和细菌的能力。然而,很少有相关研究系统地说明SCB在治疗乳腺炎中的作用。本研究的目的是证明SCB在治疗金黄色葡萄球菌引起的乳腺炎中减轻乳腺病理损伤的机制。H&E染色用于鉴别乳腺炎的病理变化和损伤。ELISA检测与炎症相关的细胞因子水平。通过蛋白质印迹分析和铁测定试剂盒检测与铁凋亡和Nrf2信号通路相关的关键信号。与对照组相比,炎症相关因子，如IL-1β，TNF-α,MPO活动,在金黄色葡萄球菌治疗的小鼠中显著增加。然而,这些变化被SCB抑制。铁凋亡相关因子Fe2+和MDA显著增加,GSH,GPX4和铁蛋白表达在金黄色葡萄球菌处理的小鼠中显著降低。SCB处理可以减弱金黄色葡萄球菌诱导的铁凋亡。此外，SCB增加SIRT1和SLC7A11表达，下调p53表达和NF-κB激活。总之,SCB通过上调SIRT1/p53/SLC7A11信号通路减轻金黄色葡萄球菌诱导的乳腺炎,减弱乳腺组织中炎症相关细胞因子的激活和铁凋亡。
