| 引用本文: | 胡慧明,官扬,翁家俊,陈金平,吴茂兰,崔粲,邵峰,朱彦陈.山楂叶黄酮对高脂血症小鼠的调脂保肝作用及其对肝组织HMGCR、LDLR表达的影响[J].中国现代应用药学,2020,37(21):2599-2604. |
| HU Huiming,GUAN Yang,WENG Jiajun,CHEN Jinping,WU Maolan,CUI Can,SHAO Feng,ZHU Yanchen.Effects of Hawthorn Leaf Flavonoids on Regulating Lipid and Protecting Liver and the Expression of HMGCR and LDLR in Hyperlipidemia Mice[J].Chin J Mod Appl Pharm(中国现代应用药学),2020,37(21):2599-2604. |
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| 山楂叶黄酮对高脂血症小鼠的调脂保肝作用及其对肝组织HMGCR、LDLR表达的影响 |
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胡慧明1, 官扬1, 翁家俊1, 陈金平1, 吴茂兰1, 崔粲1, 邵峰2, 朱彦陈3
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1.江西中医药大学科技学院, 南昌 330004;2.江西中医药大学现代中药制剂教育部重点实验室, 南昌 330004;3.江西中医药大学计算机学院, 南昌 330004
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| 摘要: |
| 目的 观察山楂叶黄酮（hawthorn leaf flavonoids，HLF）对实验性高脂血症模型小鼠血脂水平、肝功能及、羟甲基戊二酰辅酶A还原酶（HMG-CoA reductase，HMGCR）、低密度脂蛋白受体（low density lipoprotein receptor，LDLR）表达的影响。方法 KM小鼠50只，随机分为正常对照组、模型对照组、HLF低剂量组（1.5 g·kg-1）、HLF高剂量组（3.0 g·kg-1）、辛伐他汀组，每组10只。正常对照组给予基础饲料，其他各组给予高脂饲料，实验期间自由采食饮水，各组灌胃给予相应药物，连续5周。分别于造模给药2周、5周后，各组小鼠眼眶取血检测总胆固醇（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）、天冬氨酸氨基转移酶（AST）及丙氨酸氨基转移酶（ALT）水平，末次给药采血后解剖取肝脏，HE染色法观察小鼠肝组织病理形态学变化，免疫组化法检测肝组织HMGCR、LDLR的表达水平。结果 与正常对照组比较，造模5周后，模型对照组小鼠血清TC、TG、LDL-C、ALT及AST显著升高，HDL-C显著降低，肝脏脂肪变性明显，肝组织HMGCR表达水平升高、LDLR表达水平下降。与模型对照组比较，给药5周后，HLF 1.5，3.0 g·kg-1剂量组小鼠血清TC、TG、LDL-C、ALT及AST显著降低，HDL-C显著升高，肝组织病理变化均改善，肝组织HMGCR表达水平下降、LDLR表达水平升高，其中以3.0 g·kg-1更为显著。结论 HLF能降低高脂血症模型小鼠血脂水平，改善肝功能，减轻肝脏脂肪病变，其作用机制可能是通过下调HMGCR表达抑制胆固醇生物合成，并上调LDLR表达促进胆固醇的代谢，进而调节脂质代谢紊乱。 |
| 关键词: 高脂血症 山楂叶黄酮 血脂 肝功能 羟甲基戊二酰辅酶A还原酶 低密度脂蛋白受体 |
| DOI：10.13748/j.cnki.issn1007-7693.2020.21.007 |
| 分类号:R965.1 |
| 基金项目:江西省重点研发计划项目（20201BBG71005）；江西省自然（青年）科学基金项目（20202BABL216072）；江西省卫生计生委中医药科研计划（2018A340，2018A341）；江西省药品监督管理局科研项目（2019JS20） |
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| Effects of Hawthorn Leaf Flavonoids on Regulating Lipid and Protecting Liver and the Expression of HMGCR and LDLR in Hyperlipidemia Mice |
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HU Huiming1, GUAN Yang1, WENG Jiajun1, CHEN Jinping1, WU Maolan1, CUI Can1, SHAO Feng2, ZHU Yanchen3
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1.College of Science and Technology, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China;2.Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China;3.College of Computer Science, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
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| Abstract: |
| OBJECTIVE To observe the effects of hawthorn leaf flavonoids(HLF) on regulating lipid and protecting liver and the expression of HMG-CoA reductase(HMGCR) and low density lipoprotein receptor(LDLR) in hyperlipidemia mice. METHODS Fifty KM mice were randomly divided into the normal control group, model control group, low dose(1.5 g·kg-1) and high dose(3.0 g·kg-1) of HLF groups, simvastatin group. Except the normal control group fed basic food, the other groups were given high-fat diet. During the experiment, all mice free drunk water for 5 weeks. Animals were administered with corresponding drugs for 5 weeks. The blood was collected after the administration 2 weeks and 5 weeks respectively from the orbit to detect total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C), aspartate aminotransferase(AST) and alanine aminotransferase (ALT) levels. The liver was dissected after the last administration of blood sampling to observe the histopathological changes of the liver tissues by HE staining. The expression levels of HMGCR and LDLR in the liver tissues were detected by immunohistochemistry. RESULTS Compared with the normal control group, serum levels of TC, TG, LDL-C, ALT and AST were significantly increased while HDL-C level was decreased in the model control group whose the expression level of HMGCR was significantly increased in liver tissue after the modeling 5 weeks, and liver steatosis was severe. Meanwhile, the expression level of LDLR in liver tissue was significantly reduced in the model control group. Compared with the model group, serum levels of TC, TG, LDL-C, ALT and AST were significantly decreased while HDL-C level was increased in HLF 1.5 and 3.0 g·kg-1 doses of groups whose the expression level of HMGCR was significantly reduced in liver tissue after the administratin of 5 weeks. Meanwhile, the expression level of LDLR in liver tissue was significantly increased in HLF group. The effect was more significant in 3.0 g·kg-1 group than 1.5 g·kg-1. The liver tissue in the model group showed fatty degeneration, while pathological changes of liver tissue were improved in HLF different doses of groups. CONCLUSION The HLF can reduce blood lipid level, improve liver function and reduce liver steatosis in hyperlipidemia model mice, which suggested that it has better function of regulating lipid and protecting liver. The mechanism might be related to the down-regulation of HMGCR expression to inhibit cholesterol biosynthesis and up-regulating of LDLR expression to promote cholesterol metabolism, which regulate lipid metabolism disorder. |
| Key words: hyperlipidemia hawthorn leaf flavonoids blood lipid liver function HMG-CoA reductase low density lipoprotein receptor |
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