丹红化瘀口服液通过 Sirtuin 1/NF-κB 信号通路抗炎防治静脉血栓。
Danhong Huayu Koufuye prevents venous thrombosis through antiinflammation via Sirtuin 1/NF-κB signaling pathway.
机构信息
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
Guangzhou Baiyun Mountain and Hutchison Whampoa Ltd., Guangzhou, Guangdong, 510515, China.
出版信息
J Ethnopharmacol. 2019 Sep 15;241:111975. doi: 10.1016/j.jep.2019.111975. Epub 2019 May 26.
ETHNOPHARMACOLOGICAL RELEVANCE
Danhong Huayu Koufuye (DHK), a compound traditional Chinese medicine, is composed of Salvia miltiorrhiza radix (Salvia miltiorrhiza Bge.), Angelicae Sinensis radix (Angelicae Sinensis (Oliv.) Diels.), Chuanxiong rhizoma (Ligusticum chuanxiong Hort.), Persicae semen (Prunus persica (L.) Batsch), Carthami flos (Carthamus tinctorius L.), Bupleuri radix (Bupleurum chinense DC.) and Aurantii fructus (Citrus aurantium L.). DHK prevents deep vein thrombosis (DVT) through antiinflammation. However, the antiinflammatory mechanism of DHK is still unknown.
OBJECTIVE
The aim of this study was to evaluate whether DHK prevented venous thrombosis through antiinflammation via Sirtuin 1 (SIRT1)/NF-κB signaling pathway.
METHODS
Inferior vena cava (IVC) stenosis-induced DVT rat model was established. Rats were administered with DHK (1.6, 3.2 or 6.4 mL/kg/d, p.o.), heparin (200 U/kg/d, i.v.), clopidogrel (25 mg/kg/d, p.o.), resveratrol (50 mg/kg/d, p.o.) or vehicle (p.o.) once daily for two days. Blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts and platelet activity were evaluated. Serum levels of inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay. Pathological changes were observed by hematoxylin-eosin (HE) staining. Protein expressions in thrombosed IVCs were evaluated by Western blot and/or immunofluorescence analyses. SIRT1 mRNA expression was analyzed by real-time quantitative polymerase chain reaction. Besides, SIRT1-specific inhibitor EX527 was pretreated to confirm the role of SIRT1/NF-κB signaling pathway in the antithrombotic effect of DHK.
RESULTS
DHK remarkably prevented DVT. DHK had no effects on blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts or platelet activity. But DHK significantly up-regulated protein and mRNA expressions of SIRT1, and reduced leukocytes infiltration into thrombus and vein wall, serum levels of inflammatory cytokines, and protein expressions of acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF). Moreover, the antithrombotic effect of DHK was significantly abolished by EX527.
CONCLUSION
DHK may prevent DVT by inhibiting inflammation via SIRT1/NF-κB signaling pathway.
丹红化瘀口服液通过抗炎预防深静脉血栓形成
丹红化瘀口服液（DHK）是一种复方中药，由丹参、当归、川芎、桃仁、红花、柴胡和陈皮组成。DHK 通过抗炎预防深静脉血栓形成（DVT）。然而，DHK 的抗炎机制尚不清楚。
目的
本研究旨在评估 DHK 是否通过 Sirtuin 1（SIRT1）/NF-κB 信号通路预防静脉血栓形成。
方法
建立下腔静脉（IVC）狭窄诱导的 DVT 大鼠模型。大鼠每天口服 DHK（1.6、3.2 或 6.4 mL/kg/d）、肝素（200 U/kg/d，iv）、氯吡格雷（25 mg/kg/d，po）、白藜芦醇（50 mg/kg/d，po）或载体（po）一次，连续两天。评估血液凝固、血液纤溶、血液黏度、血细胞计数和血小板活性。通过酶联免疫吸附试验分析血清炎症细胞因子水平。通过苏木精-伊红（HE）染色观察病理变化。通过 Western blot 和/或免疫荧光分析评估血栓形成 IVC 中的蛋白表达。通过实时定量聚合酶链反应分析 SIRT1 mRNA 表达。此外，用 SIRT1 特异性抑制剂 EX527 预处理以确认 SIRT1/NF-κB 信号通路在 DHK 抗血栓形成作用中的作用。
结果
DHK 显著预防 DVT。DHK 对血液凝固、血液纤溶、血液黏度、血细胞计数或血小板活性没有影响。但 DHK 显著上调 SIRT1 蛋白和 mRNA 表达，减少白细胞浸润血栓和静脉壁，降低血清炎症细胞因子水平，下调乙酰化 p65（Ace-p65）、磷酸化 p65（p-p65）和组织因子（TF）蛋白表达。此外，EX527 显著消除了 DHK 的抗血栓形成作用。
结论
DHK 可能通过 SIRT1/NF-κB 信号通路抑制炎症来预防 DVT。
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