Zhejiang Chinese Medical University, Hangzhou, 310053, China.
J Ethnopharmacol. 2021 Jun 28;274:114058. doi: 10.1016/j.jep.2021.114058. Epub 2021 Mar 23.
Danhong injection (DHI) is a Chinese medical injection applied to the clinical treatment of cardiovascular diseases that has anti-inflammatory, antiplatelet aggregation and antithrombotic effects. This study aimed to explore the effects of DHI on dyslipidemia and cholesterol metabolism in high-fat diet-fed rats.
Sprague Dawley (SD) rats were randomly divided into six groups: normal group (Normal); hyperlipidemia model group (Model); DHI-treated groups at doses of 1.0 mL/kg, 2.0 mL/kg, 4.0 mL/kg; and simvastatin positive control group (2.0 mg/kg). The hypolipidemic effects of DHI were evaluated by measuring serum lipid levels, hepatic function and oxidative stress, respectively. And pathological changes in liver tissues were determined using hematoxylin-eosin (H&E) and oil red O staining. Moreover, the mRNA and protein expression levels of cholesterol metabolism related genes were detected by real-time PCR (RT-PCR) and Western blot.
Compared with the Model group, DHI treatment markedly decreased the liver index and improved the pathological morphology of liver tissues. DHI treatment dose-dependently decreased the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), and free fatty acids (FFA) in serum or liver tissues (P < 0.01 or P < 0.05), and increased the high-density lipoprotein cholesterol (HDL-C) and tripeptide glutathione (GSH) (P < 0.01 or P < 0.05). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were increased in the DHI-treated groups (P < 0.01 or P < 0.05), while the alanine transaminase (ALT) and aspartate transaminase (AST) were decreased (P < 0.01 or P < 0.05). Furthermore, the expression levels of LDL receptor (LDLR), cholesterol 7-α-hydroxylase (CYP7A1), liver X receptor α (LXRα), and peroxisome proliferator-activated receptor α (PPARα) were dose-dependently upregulated in the DHI-treated groups, whereas the expression of sterol regulatory element-binding protein-2 (SREBP-2) was downregulated.
Our study demonstrated that DHI markedly ameliorated hyperlipidemia rats by regulating serum lipid levels, inhibiting hepatic lipid accumulation and steatosis, improving hepatic dysfunction, and reducing oxidative stress. The potential mechanism was also tentatively investigated and may be related to the promotion of bile acid synthesis via activation of the PPARα-LXRα-CYP7A1 pathway. Therefore, DHI could be regarded as a potential hypolipidemic drug for the treatment of hyperlipidemia.
丹红注射液（DHI）是一种应用于心血管疾病临床治疗的中药注射液，具有抗炎、抗血小板聚集和抗血栓形成的作用。本研究旨在探讨 DHI 对高脂饮食喂养大鼠血脂异常和胆固醇代谢的影响。
将 Sprague Dawley（SD）大鼠随机分为六组：正常组（Normal）；高脂血症模型组（Model）；DHI 处理组剂量为 1.0 mL/kg、2.0 mL/kg、4.0 mL/kg；和辛伐他汀阳性对照组（2.0 mg/kg）。通过测量血清脂质水平、肝功能和氧化应激，分别评估 DHI 的降血脂作用。并用苏木精-伊红（H&E）和油红 O 染色法测定肝组织的病理变化。此外，通过实时 PCR（RT-PCR）和 Western blot 检测胆固醇代谢相关基因的 mRNA 和蛋白表达水平。
与模型组相比，DHI 处理显著降低了肝指数，改善了肝组织的病理形态。DHI 处理剂量依赖性地降低了血清或肝组织中总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、丙二醛（MDA）和游离脂肪酸（FFA）的水平（P < 0.01 或 P < 0.05），并增加了高密度脂蛋白胆固醇（HDL-C）和三肽谷胱甘肽（GSH）的水平（P < 0.01 或 P < 0.05）。DHI 处理组中超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）的活性增加（P < 0.01 或 P < 0.05），而丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）则降低（P < 0.01 或 P < 0.05）。此外，DHI 处理组 LDL 受体（LDLR）、胆固醇 7-α-羟化酶（CYP7A1）、肝 X 受体 α（LXRα）和过氧化物酶体增殖物激活受体 α（PPARα）的表达水平呈剂量依赖性上调，而固醇调节元件结合蛋白-2（SREBP-2）的表达水平下调。
本研究表明，DHI 通过调节血清脂质水平、抑制肝内脂质堆积和脂肪变性、改善肝功能和减轻氧化应激，显著改善了高脂血症大鼠的高脂血症。还初步探讨了其潜在机制，可能与通过激活 PPARα-LXRα-CYP7A1 途径促进胆汁酸合成有关。因此，DHI 可作为治疗高脂血症的潜在降脂药物。
