Liu Hui-Fang, Huang Jian-Bo, Huang Min-Cong, Jiang Tao, Lyu Gui-Yuan, Li Bo, Qiu Xin-Yu, Cheng Bin, Lou Zhao-Huan
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University Hangzhou 310053, China.
School of Basic Medical Sciences, Zhejiang Chinese Medical University Hangzhou 310053, China.
Zhongguo Zhong Yao Za Zhi. 2021 Apr;46(7):1795-1802. doi: 10.19540/j.cnki.cjcmm.20200104.401.
This article aims to investigate the ameliorative effect of Linderae Radix ethanol extract on hyperlipidemia rats induced by high-fat diet and to explore its possible mechanism from the perspective of reverse cholesterol transport(RCT). SD rats were divided into normal group, model group, atorvastatin group, Linderae Radix ethanol extract(LREE) of high, medium, low dose groups. Except for the normal group, the other groups were fed with a high-fat diet to establish hyperlipidemia rat models; the normal group and the model group were given pure water, while each administration group was given corresponding drugs by gavage once a day for five weeks. Serum total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-c), low density lipoprotein-cholesterol(LDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) levels were measured by automatic blood biochemistry analyzer; the contents of TC, TG, total bile acid(TBA) in liver and TC and TBA in feces of rats were detected by enzyme colorimetry. HE staining was used to observe the liver tissue lesions; immunohistochemistry was used to detect the expression of ATP-binding cassette G8(ABCG8) in small intestine; Western blot and immunohistochemistry were used to detect the expression of peroxisome proliferator-activated receptor gamma/aerfa(PPARγ/α), liver X receptor-α(LXRα), ATP-binding cassette A1(ABCA1) pathway protein and scavenger receptor class B type Ⅰ(SR-BⅠ) in liver. The results showed that LREE could effectively reduce serum and liver TC, TG levels, serum LDL-c levels and AST activity, and increase HDL-c levels, but did not significant improve ALT activity and liver index; HE staining results showed that LREE could reduce liver lipid deposition and inflammatory cell infiltration. In addition, LREE also increased the contents of fecal TC and TBA, and up-regulated the protein expressions of ABCG8 in small intestine and PPARγ/α, SR-BⅠ, LXRα, and ABCA1 in liver. LREE served as a positive role on hyperlipidemia model rats induced by high-fat diet, which might be related to the regulation of RCT, the promotion of the conversion of cholesterol to the liver and bile acids, and the intestinal excretion of cholesterol and bile acids. RCT regulation might be a potential mechanism of LREE against hyperlipidemia.
本文旨在研究乌药乙醇提取物对高脂饮食诱导的高脂血症大鼠的改善作用，并从逆向胆固醇转运（RCT）角度探讨其可能机制。将SD大鼠分为正常组、模型组、阿托伐他汀组、乌药乙醇提取物高、中、低剂量组。除正常组外，其他组给予高脂饮食以建立高脂血症大鼠模型；正常组和模型组给予纯水，各给药组每天灌胃相应药物一次，持续五周。用自动血液生化分析仪检测血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-c）、低密度脂蛋白胆固醇（LDL-c）、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平；用酶比色法检测大鼠肝脏中TC、TG、总胆汁酸（TBA）以及粪便中TC和TBA的含量。采用HE染色观察肝组织病变；用免疫组织化学法检测小肠中ATP结合盒转运体G8（ABCG8）的表达；用蛋白质免疫印迹法和免疫组织化学法检测肝脏中过氧化物酶体增殖物激活受体γ/α（PPARγ/α）、肝X受体-α（LXRα）、ATP结合盒转运体A1（ABCA1）通路蛋白及Ⅰ型清道夫受体B（SR-BⅠ）的表达。结果显示，乌药乙醇提取物可有效降低血清和肝脏TC、TG水平、血清LDL-c水平及AST活性，升高HDL-c水平，但对ALT活性和肝脏指数改善不明显；HE染色结果表明，乌药乙醇提取物可减少肝脏脂质沉积和炎性细胞浸润。此外，乌药乙醇提取物还可增加粪便中TC和TBA含量，上调小肠中ABCG8及肝脏中PPARγ/α、SR-BⅠ、LXRα和ABCA1的蛋白表达。乌药乙醇提取物对高脂饮食诱导的高脂血症模型大鼠具有积极作用，这可能与其对RCT的调节、促进胆固醇向肝脏和胆汁酸的转化以及胆固醇和胆汁酸的肠道排泄有关。RCT调节可能是乌药乙醇提取物抗高脂血症的潜在机制。
