Salvianolic acid A suppresses CCl4-induced liver fibrosis through regulating the Nrf2/HO-1, NF-κB/IκBα, p38 MAPK, and JAK1/STAT3 signaling pathways
Salvianolic acid A suppresses CCl4-induced liver fibrosis through regulating the Nrf2/HO-1, NF-κB/IκBα, p38 MAPK, and JAK1/STAT3 signaling pathways
复制标题
DOI：
10.1080/01480545.2022.2028822
复制
发表时间：
2022-01-20
影响因子：
2.6
通讯作者：
Yuan, Yongfang
中科院分区：
文献类型：
--
作者：
Li, Shengnan;Wang, Rong;Yuan, Yongfang
丹酚酸A(SA-A)是一种从中草药丹参中提取的水溶性化合物，对四氯化碳(CCl4)诱导的肝纤维化具有抗纤维化作用。然而，其潜在的分子机制仍不清楚。因此，本研究旨在阐明SA-A抗CCl4诱导的小鼠肝纤维化的分子机制。所有小鼠(对照组除外)均经腹腔注射溶于花生油的CCl4诱导肝纤维化。治疗组予SA-A(20 mg/kg或40 mg/kg)灌胃。检测肝功能指标、肝纤维化指标、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)水平。苏木精-伊红染色和Masson‘s三色染色观察肝组织病理变化。用免疫荧光法检测α-平滑肌肌动蛋白(α-SMA)和I型胶原的表达，用定量聚合酶链式反应测定炎症因子的mRNA水平。Western blotting和免疫荧光检测Nrf2/HO-1、核因子-kappaB/I kappaBα、p38MAPK和JAK1/STAT3信号通路相关蛋白的表达水平。结果表明，SA-A能减轻CCl_4诱导的肝损伤和肝纤维化，改善肝组织的形态，减轻肝纤维化中胶原的沉积。此外，SA-A还可调节肝纤维化大鼠肝组织中Nrf2/HO-1、NF-kappaB/I kappaBα、p38MAPK和JAK1/STAT3信号转导通路，提高肝组织中超氧化物歧化酶和谷胱甘肽过氧化物酶活性，降低丙二醛含量。总之，我们的研究结果表明，SA-A通过调节Nrf2/HO-1、NF-kappa B/I kappa Bα、p38MAPK和JAK1/STAT3信号通路来抑制炎症和氧化应激，从而有效地预防小鼠肝纤维化。
Salvianolic acid A (SA-A), a water-soluble compound extracted from traditional Chinese herb Radix Salvia miltiorrhiza, has anti-fibrotic effects on carbon tetrachloride (CCl4)-induced liver fibrosis. However, the underlying molecular mechanism remains unclear. Thus, this study aimed to elucidate the molecular mechanism underlying the anti-fibrotic effects of SA-A on CCl4-induced liver fibrosis in mice. All mice (except control group) were intraperitoneally administered CCl4 dissolved in peanut oil to induce liver fibrosis. Treatment groups were then gavaged with SA-A (20 or 40 mg/kg). The liver function index; liver fibrosis index; and superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were determined. Furthermore, histopathological changes in liver tissues were observed via hematoxylin-eosin and Masson's trichrome staining. The expression of alpha-smooth muscle actin (alpha-SMA) and collagen I was detected using immunofluorescence, and the mRNA levels of inflammatory factors were determined using quantitative polymerase chain reaction. Finally, western blotting and immunofluorescence were used to determine the expression levels of proteins related to Nrf2/HO-1, NF-kappa B/I kappa B alpha, p38 MAPK, and JAK1/STAT3 signaling pathways. The results showed that SA-A could ameliorate CCl4-induced liver injury and liver fibrosis, improve morphology, and alleviate collagen deposition in the fibrotic liver. Moreover, SA-A could regulate the Nrf2/HO-1, NF-kappa B/I kappa B alpha, p38 MAPK, and JAK1/STAT3 signaling pathways; increase the levels of SOD and GSH-Px; and decrease MDA level in the fibrotic liver. Collectively, our study findings indicate that SA-A is effective in preventing liver fibrosis in mice by inhibiting inflammation and oxidative stress via regulating the Nrf2/HO-1, NF-kappa B/I kappa B alpha, p38 MAPK, and JAK1/STAT3 signaling pathways.