Mai Zhen-Hao, Huang Yu, Huang Di, Huang Zi-Sheng, He Zhi-Xiang, Li Pei-Lin, Zhang Shuai, Weng Jie-Feng, Gu Wei-Li
Department of Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, No.1 Panfu Road, Yuexiu District, Guangzhou, Guangdong 518180, People's Republic of China.
Guangzhou Medical University, Guangzhou, Guangdong 510180, People's Republic of China.
Open Life Sci. 2020 Sep 15;15(1):696-710. doi: 10.1515/biol-2020-0059. eCollection 2020.
This study investigated the anti-fibrotic effects of reversine and Chinese medicine Xiang-Sha-Liu-Jun-Zi decoction (XSLJZD) on thioacetamide (TAA)-induced hepatic injury. Sprague-Dawley rats were intraperitoneally administered with TAA, then injected with reversine intraperitoneally, and/or orally provided with XSLJZD. TAA resulted in liver injury with increases in the liver index and levels of serum aspartate aminotransferase (AST) and alanine aminotransferase. Reversine alleviated the liver index and AST level and improved TAA-induced pathological changes but decreased TAA-induced collagen deposition, and α-smooth muscle actin and transforming growth factor-β1 expression. Reversine also modulated the mRNA levels of inflammatory cytokines, such as RelA, interleukin (IL)-17A, IL-22, IL-1β, IL-6, NLR family pyrin domain containing 3, platelet-derived growth factor, and monocyte chemoattractant protein, and suppressed nuclear factor (NF)-κB (p65) phosphorylation and caspase 1 activation. Meanwhile, XSLJZD protected TAA-injured liver without increasing fibrosis and enhanced the regulating effect of reversine on RelA, IL-17A, IL-1β, and MCP-1 cytokines. In conclusion, reversine ameliorates liver injury and inhibits inflammation reaction by regulating NF-κB, and XSLJZD protects the liver through its synergistic effect with reversine on regulating inflammatory cytokines.
本研究探讨了雷佛菌素和中药香砂六君子汤(XSLJZD)对硫代乙酰胺(TAA)诱导的肝损伤的抗纤维化作用。将Sprague-Dawley大鼠腹腔注射TAA,然后腹腔注射雷佛菌素,和/或口服给予XSLJZD。TAA导致肝损伤,肝指数以及血清天冬氨酸转氨酶(AST)和丙氨酸转氨酶水平升高。雷佛菌素减轻了肝指数和AST水平,改善了TAA诱导的病理变化,但减少了TAA诱导的胶原蛋白沉积以及α-平滑肌肌动蛋白和转化生长因子-β1的表达。雷佛菌素还调节了炎性细胞因子的mRNA水平,如RelA、白细胞介素(IL)-17A、IL-22、IL-1β、IL-6、含NLR家族pyrin结构域3、血小板衍生生长因子和单核细胞趋化蛋白,并抑制了核因子(NF)-κB(p65)磷酸化和半胱天冬酶1激活。同时,XSLJZD保护TAA损伤的肝脏而不增加纤维化,并增强了雷佛菌素对RelA、IL-17A、IL-1β和MCP-1细胞因子的调节作用。总之,雷佛菌素通过调节NF-κB改善肝损伤并抑制炎症反应,而XSLJZD通过与雷佛菌素协同调节炎性细胞因子来保护肝脏。