| 蒿甲醚对C57BL/Ks J-db/db小鼠糖脂代谢的影响 |
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| 引用本文： | 姜宏卫,符玮,马瑜瑾,李利平,付留俊,刘婕,彭慧芳,张颖裕,郭宇,张知音,李佳熙.蒿甲醚对C57BL/Ks J-db/db小鼠糖脂代谢的影响[J].中草药,2019,50(2):481-490. |
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| 作者姓名： | 姜宏卫 符玮 马瑜瑾 李利平 付留俊 刘婕 彭慧芳 张颖裕 郭宇 张知音 李佳熙 |
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| 作者单位： | 河南科技大学第一附属医院 内分泌科, 河南科技大学临床医学院, 河南洛阳 471003;国家代谢病临床医学研究中心分中心 洛阳市内分泌代谢病临床医学研究中心, 河南洛阳 471003;河南科技大学第一附属医院 糖尿病肾病研究院士工作站, 河南洛阳 471003,河南科技大学第一附属医院 内分泌科, 河南科技大学临床医学院, 河南洛阳 471003;国家代谢病临床医学研究中心分中心 洛阳市内分泌代谢病临床医学研究中心, 河南洛阳 471003;河南科技大学第一附属医院 糖尿病肾病研究院士工作站, 河南洛阳 471003,河南科技大学第一附属医院 内分泌科, 河南科技大学临床医学院, 河南洛阳 471003;国家代谢病临床医学研究中心分中心 洛阳市内分泌代谢病临床医学研究中心, 河南洛阳 471003;河南科技大学第一附属医院 糖尿病肾病研究院士工作站, 河南洛阳 471003,河南科技大学第一附属医院 内分泌科, 河南科技大学临床医学院, 河南洛阳 471003;国家代谢病临床医学研究中心分中心 洛阳市内分泌代谢病临床医学研究中心, 河南洛阳 471003;河南科技大学第一附属医院 糖尿病肾病研究院士工作站, 河南洛阳 471003,河南科技大学第一附属医院 内分泌科, 河南科技大学临床医学院, 河南洛阳 471003;国家代谢病临床医学研究中心分中心 洛阳市内分泌代谢病临床医学研究中心, 河南洛阳 471003;河南科技大学第一附属医院 糖尿病肾病研究院士工作站, 河南洛阳 471003,河南科技大学第一附属医院 内分泌科, 河南科技大学临床医学院, 河南洛阳 471003;国家代谢病临床医学研究中心分中心 洛阳市内分泌代谢病临床医学研究中心, 河南洛阳 471003;河南科技大学第一附属医院 糖尿病肾病研究院士工作站, 河南洛阳 471003,河南科技大学第一附属医院 内分泌科, 河南科技大学临床医学院, 河南洛阳 471003;国家代谢病临床医学研究中心分中心 洛阳市内分泌代谢病临床医学研究中心, 河南洛阳 471003;河南科技大学第一附属医院 糖尿病肾病研究院士工作站, 河南洛阳 471003,河南科技大学第一附属医院 内分泌科, 河南科技大学临床医学院, 河南洛阳 471003;国家代谢病临床医学研究中心分中心 洛阳市内分泌代谢病临床医学研究中心, 河南洛阳 471003;河南科技大学第一附属医院 糖尿病肾病研究院士工作站, 河南洛阳 471003,河南科技大学第一附属医院 内分泌科, 河南科技大学临床医学院, 河南洛阳 471003;国家代谢病临床医学研究中心分中心 洛阳市内分泌代谢病临床医学研究中心, 河南洛阳 471003;河南科技大学第一附属医院 糖尿病肾病研究院士工作站, 河南洛阳 471003,河南科技大学第一附属医院 内分泌科, 河南科技大学临床医学院, 河南洛阳 471003;国家代谢病临床医学研究中心分中心 洛阳市内分泌代谢病临床医学研究中心, 河南洛阳 471003;河南科技大学第一附属医院 糖尿病肾病研究院士工作站, 河南洛阳 471003,河南科技大学第一附属医院 内分泌科, 河南科技大学临床医学院, 河南洛阳 471003;国家代谢病临床医学研究中心分中心 洛阳市内分泌代谢病临床医学研究中心, 河南洛阳 471003;河南科技大学第一附属医院 糖尿病肾病研究院士工作站, 河南洛阳 471003 |
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| 基金项目： | 国家自然科学基金资助项目（U1404805）；国家自然科学基金资助项目（81141059） |
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| 摘 要： | 目的研究蒿甲醚对db/db小鼠糖脂代谢的影响。方法取8周龄雄性C57BL/KsJ-db/db小鼠,分为模型组(ig给予1%甲基纤维素)和蒿甲醚400、200、100、50组(分别ig给予400、200、100、50 mg/kg蒿甲醚+1%甲基纤维素),每组6只。另选6只雄性C57BL/KsJ-db/+小鼠为对照组,共给药4周。每2天测量小鼠体质量;每3天检测小鼠摄食量并评估平均每日摄食量及体质量变化;每2天测定小鼠饮水量;每3天测量小鼠尿量;每7天于禁食8 h后,尾静脉采血,用罗氏血糖仪及配套试纸分别测量小鼠空腹血糖。通过葡萄糖耐量试验(IPGTT)和胰岛素耐量试验(IPITT)评估小鼠对葡萄糖的耐受力及对胰岛素的敏感性,通过生化试剂盒测定小鼠血清总胆固醇(TC)、三酰甘油(TG)、游离脂肪酸(FFA)水平。HE染色法观察小鼠胰腺和肝脏的形态改变。Westernblotting法分析小鼠肝脏中AMP活化蛋白激酶(AMPK)、葡萄糖转运蛋白体4(GLUT-4)和胰岛素受体β(IRβ)蛋白的表达。结果与对照组比较,模型组小鼠的摄食量、摄水量、尿量均明显升高(P0.001)。与模型组比较,各剂量蒿甲醚均能显著降低小鼠摄水量及尿量(P0.01、0.001);蒿甲醚400、200、100 mg/kg均能显著降低小鼠体质量及摄食量,并呈剂量依赖性(P0.05、0.01);蒿甲醚400、200、100mg/kg均显著降低小鼠空腹血糖水平,减少IPGTT的曲线下面积(AUCs),改善小鼠的胰岛素抵抗(P0.01、0.001)。与对照组比较,模型组小鼠的TC、TG及FFA水平均显著升高(P0.05)。与模型组比较,蒿甲醚可显著降低小鼠血清中的TC、TG及FFA水平,并呈剂量依赖性(P0.05);可显著改善db/db小鼠的胰岛空泡变性和肝脂肪变性,使小鼠肝脏中的AMPK、GLUT-4及IRβ蛋白表达增加(P0.05)。随着干预时间的延长,剂量越高的小鼠呈现出较高的死亡率及不良反应发生率。结论蒿甲醚可显著改善糖尿病小鼠的高脂状态及胰岛素抵抗,治疗脂肪肝,可能通过AMPK途径上调GLUT-4以及IRβ蛋白的表达发挥作用,有望用于代谢综合征为主的2型糖尿病的治疗。但较高剂量蒿甲醚及较长时间应用会导致较多不良反应的发生。
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| 关 键 词： | 蒿甲醚 不同剂量 胰岛素抵抗 AMP活化蛋白激酶 C57BL/KsJ-db/db小鼠 |
| 收稿时间： | 2018/8/21 0:00:00 |
Effects of artemether on glucose and lipid metabolism in C57BL/KsJ-db/db mice |
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| JIANG Hong-wei,FU Wei,MA Yu-jin,LI Li-ping,FU Liu-jun,LIU Jie,PENG Hui-fang,ZHANG Ying-yu,GUO Yu,ZHANG Zhi-yin and LI Jia-xi.Effects of artemether on glucose and lipid metabolism in C57BL/KsJ-db/db mice[J].Chinese Traditional and Herbal Drugs,2019,50(2):481-490. |
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| Authors: | JIANG Hong-wei FU Wei MA Yu-jin LI Li-ping FU Liu-jun LIU Jie PENG Hui-fang ZHANG Ying-yu GUO Yu ZHANG Zhi-yin and LI Jia-xi |
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| Institution: | Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China;National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Clinical Research Center of Endocrine and Metabolic Diseases, Luoyang 471003, China;Academican Workstation for Diabetic Nephropathy Disease Research of First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China,Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China;National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Clinical Research Center of Endocrine and Metabolic Diseases, Luoyang 471003, China;Academican Workstation for Diabetic Nephropathy Disease Research of First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China,Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China;National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Clinical Research Center of Endocrine and Metabolic Diseases, Luoyang 471003, China;Academican Workstation for Diabetic Nephropathy Disease Research of First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China,Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China;National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Clinical Research Center of Endocrine and Metabolic Diseases, Luoyang 471003, China;Academican Workstation for Diabetic Nephropathy Disease Research of First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China,Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China;National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Clinical Research Center of Endocrine and Metabolic Diseases, Luoyang 471003, China;Academican Workstation for Diabetic Nephropathy Disease Research of First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China,Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China;National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Clinical Research Center of Endocrine and Metabolic Diseases, Luoyang 471003, China;Academican Workstation for Diabetic Nephropathy Disease Research of First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China,Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China;National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Clinical Research Center of Endocrine and Metabolic Diseases, Luoyang 471003, China;Academican Workstation for Diabetic Nephropathy Disease Research of First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China,Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China;National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Clinical Research Center of Endocrine and Metabolic Diseases, Luoyang 471003, China;Academican Workstation for Diabetic Nephropathy Disease Research of First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China,Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China;National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Clinical Research Center of Endocrine and Metabolic Diseases, Luoyang 471003, China;Academican Workstation for Diabetic Nephropathy Disease Research of First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China,Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China;National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Clinical Research Center of Endocrine and Metabolic Diseases, Luoyang 471003, China;Academican Workstation for Diabetic Nephropathy Disease Research of First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China and Department of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China;National Center for Clinical Research of Metabolic Diseases, Luoyang Center for Clinical Research Center of Endocrine and Metabolic Diseases, Luoyang 471003, China;Academican Workstation for Diabetic Nephropathy Disease Research of First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471003, China |
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| Abstract: | |
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| Keywords: | artemether different doses insulin resistance AMPK C57BL/KsJ-db/db mice |
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