绞股蓝总皂苷治疗高胆固醇血症及其对肝损伤的保护作用
Therapeutic effects of gypenosides on hypercholesterolemia and it protective effect on liver injury
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摘要: 为探究绞股蓝总皂苷（GP）对高胆固醇血症的治疗作用及其初步机制，以及对高脂饮食及高剂量辛伐他汀所致肝脏损伤的保护作用，采用高胆固醇饮食喂养金黄仓鼠诱导高胆固醇血症模型对GP进行研究。实验动物金黄仓鼠分为空白组、高胆固醇饮食组、绞股蓝总皂苷低高剂量组（60 mg/kg、120 mg/kg）、辛伐他汀组（10 mg/kg）组，绞股蓝总皂苷与辛伐他汀联用组（120 mg/kg + 10 mg/kg）。通过动态监测药物治疗14 d和23 d的血胆固醇、肝功能等相关指标考察其药效，检测血清中前蛋白转化酶枯草溶菌素/Kexin9型（PCSK9）的分泌量并初步探究作用机制。结果显示，GP能显著降低血清低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）、三酰甘油（TG）水平和丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）的含量，提高血清高密度脂蛋白胆固醇（HDL-C）浓度，并显著降低PCSK9的分泌量。结果表明，GP对饮食诱导的高胆固醇血症具有较好的调节作用，可能与抑制PCSK9的分泌有关。此外，GP能够有效改善高脂饮食和高剂量辛伐他汀造成的肝脏损伤，为GP与他汀类药物联用起到减毒增效的作用提供了科学依据。Abstract: In order to explore the therapeutic effects and preliminary mechanism of gypenosides (GP) on hypercholesterolemia, as well as the protective effect on liver injury induced by high-dose simvastatin and high cholesterol diet (HCD), the hypercholesterolemia model of golden hamster was established by high cholesterol diet. The experimental animals were divided into blank group, model group, GP low and high dose groups (60 mg/kg, 120 mg/kg), simvastatin group (10 mg/kg), and GP high dose combined with simvastatin group (120 mg/kg + 10 mg/kg).The efficacy was investigated through dynamic monitoring serum cholesterol and liver function related indexes after drug treatment of 14 and 23 days. The results showed that GP could significantly reduce the levels of serum low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), increase the level of serum high density lipoprotein cholesterol (HDL-C), and reduce the secretion of PCSK9. It is suggested that GP has a good therapeutic effect on HCD diet-induced hypercholesterolemia hamsters, which may be related to its inhibition of PCSK9 secretion. In addition, GP can significantly ameliorate liver damage caused by HCD diet and high-dose simvastatin. These findings provide a scientific basis and useful reference for the combination of GP and statins to reduce toxicity and increase efficacy.
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Keywords:
- gypenosides /
- hypercholesterolemia /
- hepatotoxicity /
- PCSK9 /
- drug combination
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