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目的探讨荜茇宁(GBN)的衍生物(GBNT)对高脂血症大鼠的调脂作用,并考察其作用机制。方法高脂饲料喂养Wister大鼠,建立高脂血症模型,造模同时连续灌胃给药8周后,腹主动脉取血,检测各组大鼠血清中总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C),高密度脂蛋白胆固醇(HDL-C)含量;HE染色检测肝脏病理学形态;Western blot方法研究低密度脂蛋白受体(LDLR),卵磷脂胆固醇脂酰基转移酶(LCAT),胆固醇7α-羟化酶(CYP7A)蛋白表达的变化。结果GBNT低、高剂量组均能降低模型大鼠TC、TG和LDL-C的含量,升高HDL-C含量;上调LDLR,LCAT,CYP7A1蛋白的表达;并减轻肝脏脂肪变性。结论 GBNT具有降低高脂血症模型大鼠血脂水平的作用,其机制可能与调节LCAT,CYP7A1等脂质代谢酶表达有关。
Objective To investigate the lipid-regulating effect of GBNT (GBNT) on hyperlipidemic rats and its mechanism of action. Methods Wister rats were fed with high-fat diet and hyperlipidemia model was established. After continuous intragastric administration for 8 weeks, blood samples were obtained from the abdominal aorta. The levels of total cholesterol (TC), triglyceride (TG), LDL-C and HDL-C were determined by enzyme-linked immunosorbent assay (ELISA). Liver pathology was detected by HE staining. LDLR, Phospholipid cholesterol acyltransferase (LCAT), cholesterol 7α-hydroxylase (CYP7A) protein expression changes. Results Low and high doses of GBNT could decrease the levels of TC, TG and LDL-C, increase the content of HDL-C, upregulate the expression of LDLR, LCAT and CYP7A1, and alleviate hepatic steatosis. Conclusion GBNT can reduce the level of blood lipid in hyperlipidemia rats, which may be related to the regulation of lipid metabolism enzymes such as LCAT and CYP7A1.