白鹤灵芝总萘醌对高脂饮食诱导的非酒精性脂肪肝小鼠的作用研究

为评价白鹤灵芝总萘醌（Rhinacanthins-rich extract from Rhinacanthus nasutus，RRE）的降血脂及保护肝脏作用，采用高脂饲料诱导建立的非酒精性脂肪肝（Nonalcoholic Fatty Liver Disease，NAFLD）小鼠模型，通过测定小鼠血清中总胆固醇（Total Cholesterol，TC）、甘油三酯（Triglyceride，TG）、高密度脂蛋白（High Density Lipoprotein，HDL-C）、低密度脂蛋白（Low Density Lipoprotein，LDL-C）及肝脏及谷草转氨酶（Aspartate transaminase，AST）、谷丙转氨酶（Alanine transaminase，ALT）、碱性磷酸酶（Alkaline phosphatase，AKP）的水平，以及肝脏组织进行病理学观察。动物实验结果表明，RRE干预后有效改善了NAFLD小鼠肝脏病理病变进程，缓解炎性损伤，减少肝脏脂肪颗粒堆积；高、中剂量均能显著降低NAFLD小鼠血清中TC、TG、LDL-C水平（P<0.05），极显著升高HDL-C水平（P<0.01），显著降低NAFLD小鼠血清中AST、ALT、AKP活力（P<0.05或P<0.01）；其指标水平均优于熊果酸组；RRE低剂量组可显著降低NAFLD小鼠血清中TG、LDL-C、AST、水平（P<0.05），可降低TC、ALT、AKP水平，但无显著性差异（P>0.05）；通过网络药理学对白鹤灵芝与NAFLD疾病相关作用靶点进行交集，结合分子对接技术对RRE的有效活性物质及作用机制进行预测，结果表明白鹤灵芝素-C（rhinacanthin-C）与交集靶点具有良好的结合潜力。研究表明RRE有显著的降血脂、改善脂质沉积和炎性损伤、保护肝脏的作用，其作用机制可能是rhinacanthin-C经由AMPK-SREBP1c-SIRT1信号调节脂质代谢紊乱发挥作用，为壮药白鹤灵芝开发为降血脂、改善脂肪肝的民族药物提供实验依据。

Effects of Rhinacanthins-rich Extract from Rhinacanthus nasutus on Nonalcoholic Fatty Liver Rats Induced by High Fat Diet

In order to evaluate the effect of RRE on reducing blood lipid and protecting liver, a model of nonalcoholic fatty liver disease (NAFLD) mice induced by high-fat diet was used, and then the body weight, liver weight and liver coefficient of each group were calculated, and the TC、TG、HDL-C、LDL-C、AST、ALT、AKP were checked by sample test. The liver tissue was stained with HE and oil Red O for pathological observation and fat particles observation; Animal experiment results showed that RRE intervention could effectively improve the process of liver pathological changes, alleviate inflammatory injury and reduce the accumulation of liver fat particles in NAFLD mice; both high and medium doses of RRE could significantly reduce the levels of TC, TG and LDL-C in serum of NAFLD mice (P<0.05), significantly increase the level of HDL-C (P<0.01), and significantly reduce the activities of AST, ALT and AKP in serum of NAFLD mice (P<0.05 or P<0.01); The index levels were better than those of ursolic acid group; RRE low dose group could significantly reduce the levels of TG, LDL-C, AST and in serum of NAFLD mice (P<0.05), and could reduce the levels of TC, ALT and AKP, but there was no significant difference (P>0.05); Through network pharmacology, the intersection of Rhinacanthus nasutus and NAFLD disease-related targets was carried out, and the effective active substances and action mechanism of RRE were predicted combined with molecular docking technology, which showed that rhinacanthin-C had good binding potential with the intersection targets. The experimental results showed that the RRE could reduce blood lipid, improved liver lipid deposition and inflammatory injury in NAFLD mice, so as to protect the liver. Its mechanism may be that the active substance rhinacanthin-C can improve liver lipid deposition and metabolic disorder through AMPK-SREBP1c-SIRT1 signal pathway. The experimental results can provide a scientific basis for the development of Zhuang medicine Rhinacanthus nasutus as a national drug for reducing blood lipid and improving fatty liver.