Department of Pharmacology, School of Basic Medicine, Hebei Medical University, 326, Xinshi South Road, Shijiazhuang 050091, Hebei, China.
J Ethnopharmacol. 2013 Jul 9;148(2):671-81. doi: 10.1016/j.jep.2013.05.028. Epub 2013 May 22.
Salvia miltiorrhiza (SM, also known as Danshen) is a well-known Chinese medicinal herb, which has shown hepatoprotective effects with anti-fibrotic, anti-oxidative, anti-inflammatory and anti-apoptotic properties. To explore the effects and potential mechanism of SM against hepatic fibrosis induced by chronic iron overload in mice.
Sixty male mice were randomized into five groups (n=12 in each group): control (saline), iron overload, iron overload with low-dose SM (3g/kg/day), iron overload with high-dose SM (6g/kg/day) and iron overload with deferoxamine (100mg/kg/day) groups. The iron overload model was established by intraperitoneal injection with iron dextran at 50mg/kg body weight/day, and the entire course lasted for 7 weeks. The major constituents of SM injection were quantified by high performance liquid chromatography. Changes of hepatic iron, hydroxyproline (Hyp), glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) were assayed by standard procedures. Protein expression levels of type I collagen, type III collagen, tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α) were analyzed by immunohistochemistry, and mRNA levels of transforming growth factor-β (TGF-β), matrix metal proteinase-9 (MMP-9) and caspase-3 were detected by RT-PCR. Morphological changes were observed with Prussian blue, Masson's trichrome and hematoxylin-eosin staining.
Treatment of chronic iron-overloaded mice with SM dose-dependently ameliorated changes in hepatic morphology and coefficient, reduced iron deposition and Hyp content, suppressed overexpression of type I collagen and type III collagen, downregulated expression of TGF-β mRNA, and upregulated expression of MMP-9 mRNA in the liver. Moreover, SM treatment contributed to decreased MDA content, increased SOD activity and GSH content, while it reduced expression of TNF-α, IL-1α and caspase-3.
SM displayed anti-fibrotic activity in the liver induced by chronic iron overload, which may be attributed to multitargeted inhibition of iron deposition and collagen accumulation, as well as oxidative stress, inflammation and apoptosis.
丹参（SM，也称为丹参）是一种著名的中药，具有抗纤维化、抗氧化、抗炎和抗细胞凋亡作用，显示出对肝纤维化的保护作用。本研究旨在探讨 SM 对慢性铁过载诱导的小鼠肝纤维化的作用及潜在机制。
60 只雄性小鼠随机分为五组（每组 12 只）：对照组（生理盐水）、铁过载组、铁过载低剂量 SM 组（3g/kg/天）、铁过载高剂量 SM 组（6g/kg/天）和铁过载去铁胺组（100mg/kg/天）。采用腹腔注射铁右旋糖苷 50mg/kg 体重/天建立铁过载模型，整个过程持续 7 周。采用高效液相色谱法测定 SM 注射液的主要成分含量。采用标准方法测定肝铁、羟脯氨酸（Hyp）、谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和丙二醛（MDA）的变化。采用免疫组化法分析 I 型胶原、III 型胶原、肿瘤坏死因子-α（TNF-α）和白细胞介素-1α（IL-1α）的蛋白表达水平，采用 RT-PCR 检测转化生长因子-β（TGF-β）、基质金属蛋白酶-9（MMP-9）和半胱氨酸天冬氨酸蛋白酶-3（caspase-3）的 mRNA 水平。采用普鲁士蓝、马松三色和苏木精-伊红染色观察形态学变化。
SM 剂量依赖性地改善慢性铁过载小鼠的肝形态和系数变化，减少铁沉积和 Hyp 含量，抑制 I 型胶原和 III 型胶原的过度表达，下调 TGF-βmRNA 的表达，上调 MMP-9mRNA 的表达。此外，SM 治疗有助于降低 MDA 含量，增加 SOD 活性和 GSH 含量，同时降低 TNF-α、IL-1α和 caspase-3 的表达。
SM 对慢性铁过载诱导的肝纤维化具有抗纤维化活性，这可能归因于铁沉积和胶原堆积、氧化应激、炎症和细胞凋亡的多靶点抑制。
