西洋参改善IR的作用及其机制研究
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摘要
胰岛素抵抗(insulin resistance,IR)是指机体靶器官或组织对胰岛素生物效应的敏感性降低或丧失而产生的一系列病理生理改变。近年来随着人们生活方式和饮食结构的改变,2型糖尿病、高血压、肥胖、血脂紊乱和动脉粥样硬化等疾病的发病率逐年升高,而IR被认为是以上各种疾病同时并存和共同联系的基础。所以,IR成为近年来医学领域的一个研究热点。尽管众多学者对IR的研究较为深入,但迄今为止,仍没有一种被大家公认的治疗IR的理想药物。中药的作用机制具有多途径、多环节、多靶点的特点,通过降糖、调脂、纠正代谢紊乱等途径治疗一些代谢性疾病时体现出独特的优势。中医学者通过整体观思想、辨证旌治方法治疗IR取得较满意的临床效果,但鲜有系统而深入地对运用中医药治疗IR作用机制进行研究者。西洋参改善IR状态,在临床上取得较为满意的疗效。本研究意在进一步阐明西洋参治疗IR的物质基础及其作用机制,从而为西洋参治疗糖尿病、高血压等与IR相关的疾病提供较为确切的理论依据。
本研究从文献研究和实验研究两个角度分别论述了中西医对IR的研究进展,且对西洋参治疗IR的物质基础和作用机制进行了较为深入的阐发。
1.文献研究:通过中国知网(www.cnki.net)、美国国家科学院会刊(www.pnas.org)、Pubmed、free medical journal等网站的资源,检索近年来与IR有关的文献报道500余篇。其中,包括目前现代医学和中医学对于IR的发病机理的认识、治疗方法和遣方用药的评价等相关文献资料:亦包括现代医学对IR的研究方法等文献报道,如实验性IR动物模型的确立与评价及肿瘤坏死因子-α、瘦素、脂联素、抵抗素等脂肪细胞因子的近期研究概况。通过对上述资料进行较为系统的总结和综述,进而掌握了有关IR研究的前沿动态。
2.实验研究
研究目的:明确西洋参改善IR的活性部位,并探讨其作用机制,为开发中药新制剂奠定基础。
研究方法:以长期高脂饮食喂养加单次小剂量链脲佐菌素(STZ)腹腔注射的方法复制IR大鼠动物模型,应用西洋参不同提取部位对其进行干预,以罗格列酮作为阳性对照药,观察药物对实验性IR大鼠糖代谢、脂代谢、胰岛素敏感性、脂肪细胞因子水平、骨骼肌葡萄糖转运蛋白-4mRNA和脂肪组织抵抗素mRNA表达等的影响。
研究结果:①模型评价:成功复制了实验性IR大鼠模型,该实验模型动物表现为高胰岛素血症、低胰岛素敏感性、胰岛素敏感指数(ISI)的绝对值明显高于正常动物,符合IR的临床特点。模型成模率较高,可操作性强,经济成本适宜,是研究IR的理想载体。②基础药效研究:在成功建立IR大鼠模型的基础上,观察西洋参不同沈脱部位对实验性IR大鼠糖、脂代谢的影响。糖代谢研究结果表明,西洋参60%醇提组、30%醇提组、水洗组、罗格列酮组均能降低IR大鼠的FBG和FINS水平,与模型组比较,有显著性差异(P＜0.01)。脂代谢指标血清生化学检测结果显示,各给药组大鼠TG、TC、FFA水平均下降。在降低血清中TG水平上,罗格列酮组、西洋参60%和30%醇提组作用显著,与模型组比较有显著性差异(P＜0.01)。在降低血清中TC水平上,除95%醇提组外,其余各组与模型组比较有差异(P＜0.05)。提示西洋参可通过降低血脂改善IR,且对TG作用明显。在降低FFA水平上,西洋参60%醇提组、30%醇提组、水洗组和罗格列酮组均能明显降低FFA含量,与模型组比较,有显著性差异(P＜0.01),且西洋参30%醇提组效果较好。③机理探讨:在基础药效学试验研究基础上,进行药物作用的机理探讨。采用放射性免疫分析方法检测各组大鼠血清中肿瘤坏死因子-α、瘦素水平:用酶联免疫法检测血清中脂联素、抵抗素水平;并用RT-PCR方法观测骨骼肌转运蛋白-4mRNA和脂肪组织抵抗素mRNA等表达的影响。实验结果显示:西洋参60%醇提组、30%醇提组、罗格列酮组均能降低IR大鼠血清中肿瘤坏死因子-α、瘦素水平、抵抗素的水平,而升高脂联素的水平,与模型组比较,分别为P＜0.05/P＜0.01。提示西洋参可通过调节脂肪细胞因子的分泌来改善实验大鼠的IR状态。同时西洋参可以上调实验大鼠骨骼肌转运蛋白-4mRNA的表达和下调其脂肪组织中抵抗素mRNA的表达,进而改善IR状态。
结论:①通过高脂饲料喂养配合单次小剂量注射STZ可成功复制IR大鼠模型。②西洋参有改善IR实验大鼠糖代谢和脂代谢的作用,其活性部位主要为30%乙醇洗脱部分及60%乙醇洗脱部分。③西洋参活性部位通过影响TNF-α、Leptin、APN、Resistin等脂肪细胞因子的表达来改善IR。④西洋参活性部位可通过上调GLUT-4mRNA的表达及下调脂肪组织中Resistin mRNA的表达而对InsR后抵抗有改善作用。
Insulin resistance(IR)means the target organs or the organizations are insensitive to the insulin,thus it decreases the biological effect of the latter and leads to a series of changes in pathology and physical function.In recent years,the cases of diabetes,hypertension, obesity,disorder of blood fat,arteriosclerosis are increased every year since the living style and dietary structure have been changed,and IR is assumed as the foundation and correlation of these diseases.So IR becomes a focus in the scientific research field.There is no medicine has been recognized as an ideal one to cure IR by most people,although researchers have studied it deeply.While herbs can cure diseases with its characteristic of various approach and target point,so they have the advantages in treating some metabolic diseases.And it has been proved from clinic by doctors of Chinese Medicine with the method of treatment based on symptoms under the guidance of holism.But the metabolism of action is retarded,for most cases lack of experimental data for complementary proof. Although American Ginseng also has been proved effective in curing IR by my tutor in clinic,there is an undiscovered metabolism to be found,and the intention of this research project is just to try to find out it and affirm the foundation of the action.
This research project covered two sides of content,one is on document research,and the other is on experimental research.
After retrieved about 500 pieces of documents pertaining to IR on the internet,we comprehend the pathogenesis,the method of treatment,and medicine or herbs commonly used on the whole,During the search course,we also learn how to establish and evaluate the IR model in rats,and get a deep comprehension in lipocyte cytokine,such as tumor necrosis factor-α(TNF-α),leptin,adiponectin(APN)and resistin etc,as well as the new research trends about them.
On the basis of above research,we carry out the experimental research.First,we set up the IR model in rats by feeding them high fat diet combining injecting small dose of STZ once to them.Secondly,we use different elution fraction group from American Ginseng to treat the IR rats compared with rosiglitazone.Thirdly,we observe the difference within each group on the side of glycometabolism,lipometabolism,insulin sensitivity,lipocyte cytokine level,mRNA of glucose transporter-4(GLUT-4)in skeletal muscle and resistin in white fat tissue.
The results of the search are that all groups of 30 percent alcohol elution fraction,60 percent alcohol elution fraction,distilled water elution fraction and rosiglitazone can decrease FBG and FINS in blood serum,and have an obvious difference with the model group.On lipometabolism aspect,all treatment groups have the effects of reducing TG,TC and FFA in blood serum.
From the results we get as mentioned above,we further discuss the action metabolism.We use method of radioimmunoassay and enzyme linked immunosorbent assay to measure TNF-α、Leptin,APN and Resistin in serum separately.As to mRNA of GLUT-4 in skeletal muscle and resistin in white fat tissue,we use RT-PCR method.From the data we obtain, we may tell American Ginseng can ameliorate IR from both lipocyte cytokine angle and gene expression angle.
At last,we draw the conclusions as follows from the research project.The first one is the IR model in rats were successfully made by high fat diet combined with injecting small dose STZ.The second one is that American Ginseng has the good effects on glycometabolism and lipometabolism,and the active site is 30 percent alcohol elution fraction,60 percent alcohol elution fraction.The third one is American Ginseng is available of ameliorating IR by affecting TNF-α、Leptin、APN and Resistin.The last one is that American Ginseng can also ameliorate IR by boosting up mRNA expression of GLUT-4 and lowering mRNA expression.
本研究从文献研究和实验研究两个角度分别论述了中西医对IR的研究进展,且对西洋参治疗IR的物质基础和作用机制进行了较为深入的阐发。
1.文献研究:通过中国知网(www.cnki.net)、美国国家科学院会刊(www.pnas.org)、Pubmed、free medical journal等网站的资源,检索近年来与IR有关的文献报道500余篇。其中,包括目前现代医学和中医学对于IR的发病机理的认识、治疗方法和遣方用药的评价等相关文献资料:亦包括现代医学对IR的研究方法等文献报道,如实验性IR动物模型的确立与评价及肿瘤坏死因子-α、瘦素、脂联素、抵抗素等脂肪细胞因子的近期研究概况。通过对上述资料进行较为系统的总结和综述,进而掌握了有关IR研究的前沿动态。
2.实验研究
研究目的:明确西洋参改善IR的活性部位,并探讨其作用机制,为开发中药新制剂奠定基础。
研究方法:以长期高脂饮食喂养加单次小剂量链脲佐菌素(STZ)腹腔注射的方法复制IR大鼠动物模型,应用西洋参不同提取部位对其进行干预,以罗格列酮作为阳性对照药,观察药物对实验性IR大鼠糖代谢、脂代谢、胰岛素敏感性、脂肪细胞因子水平、骨骼肌葡萄糖转运蛋白-4mRNA和脂肪组织抵抗素mRNA表达等的影响。
研究结果:①模型评价:成功复制了实验性IR大鼠模型,该实验模型动物表现为高胰岛素血症、低胰岛素敏感性、胰岛素敏感指数(ISI)的绝对值明显高于正常动物,符合IR的临床特点。模型成模率较高,可操作性强,经济成本适宜,是研究IR的理想载体。②基础药效研究:在成功建立IR大鼠模型的基础上,观察西洋参不同沈脱部位对实验性IR大鼠糖、脂代谢的影响。糖代谢研究结果表明,西洋参60%醇提组、30%醇提组、水洗组、罗格列酮组均能降低IR大鼠的FBG和FINS水平,与模型组比较,有显著性差异(P＜0.01)。脂代谢指标血清生化学检测结果显示,各给药组大鼠TG、TC、FFA水平均下降。在降低血清中TG水平上,罗格列酮组、西洋参60%和30%醇提组作用显著,与模型组比较有显著性差异(P＜0.01)。在降低血清中TC水平上,除95%醇提组外,其余各组与模型组比较有差异(P＜0.05)。提示西洋参可通过降低血脂改善IR,且对TG作用明显。在降低FFA水平上,西洋参60%醇提组、30%醇提组、水洗组和罗格列酮组均能明显降低FFA含量,与模型组比较,有显著性差异(P＜0.01),且西洋参30%醇提组效果较好。③机理探讨:在基础药效学试验研究基础上,进行药物作用的机理探讨。采用放射性免疫分析方法检测各组大鼠血清中肿瘤坏死因子-α、瘦素水平:用酶联免疫法检测血清中脂联素、抵抗素水平;并用RT-PCR方法观测骨骼肌转运蛋白-4mRNA和脂肪组织抵抗素mRNA等表达的影响。实验结果显示:西洋参60%醇提组、30%醇提组、罗格列酮组均能降低IR大鼠血清中肿瘤坏死因子-α、瘦素水平、抵抗素的水平,而升高脂联素的水平,与模型组比较,分别为P＜0.05/P＜0.01。提示西洋参可通过调节脂肪细胞因子的分泌来改善实验大鼠的IR状态。同时西洋参可以上调实验大鼠骨骼肌转运蛋白-4mRNA的表达和下调其脂肪组织中抵抗素mRNA的表达,进而改善IR状态。
结论:①通过高脂饲料喂养配合单次小剂量注射STZ可成功复制IR大鼠模型。②西洋参有改善IR实验大鼠糖代谢和脂代谢的作用,其活性部位主要为30%乙醇洗脱部分及60%乙醇洗脱部分。③西洋参活性部位通过影响TNF-α、Leptin、APN、Resistin等脂肪细胞因子的表达来改善IR。④西洋参活性部位可通过上调GLUT-4mRNA的表达及下调脂肪组织中Resistin mRNA的表达而对InsR后抵抗有改善作用。
Insulin resistance(IR)means the target organs or the organizations are insensitive to the insulin,thus it decreases the biological effect of the latter and leads to a series of changes in pathology and physical function.In recent years,the cases of diabetes,hypertension, obesity,disorder of blood fat,arteriosclerosis are increased every year since the living style and dietary structure have been changed,and IR is assumed as the foundation and correlation of these diseases.So IR becomes a focus in the scientific research field.There is no medicine has been recognized as an ideal one to cure IR by most people,although researchers have studied it deeply.While herbs can cure diseases with its characteristic of various approach and target point,so they have the advantages in treating some metabolic diseases.And it has been proved from clinic by doctors of Chinese Medicine with the method of treatment based on symptoms under the guidance of holism.But the metabolism of action is retarded,for most cases lack of experimental data for complementary proof. Although American Ginseng also has been proved effective in curing IR by my tutor in clinic,there is an undiscovered metabolism to be found,and the intention of this research project is just to try to find out it and affirm the foundation of the action.
This research project covered two sides of content,one is on document research,and the other is on experimental research.
After retrieved about 500 pieces of documents pertaining to IR on the internet,we comprehend the pathogenesis,the method of treatment,and medicine or herbs commonly used on the whole,During the search course,we also learn how to establish and evaluate the IR model in rats,and get a deep comprehension in lipocyte cytokine,such as tumor necrosis factor-α(TNF-α),leptin,adiponectin(APN)and resistin etc,as well as the new research trends about them.
On the basis of above research,we carry out the experimental research.First,we set up the IR model in rats by feeding them high fat diet combining injecting small dose of STZ once to them.Secondly,we use different elution fraction group from American Ginseng to treat the IR rats compared with rosiglitazone.Thirdly,we observe the difference within each group on the side of glycometabolism,lipometabolism,insulin sensitivity,lipocyte cytokine level,mRNA of glucose transporter-4(GLUT-4)in skeletal muscle and resistin in white fat tissue.
The results of the search are that all groups of 30 percent alcohol elution fraction,60 percent alcohol elution fraction,distilled water elution fraction and rosiglitazone can decrease FBG and FINS in blood serum,and have an obvious difference with the model group.On lipometabolism aspect,all treatment groups have the effects of reducing TG,TC and FFA in blood serum.
From the results we get as mentioned above,we further discuss the action metabolism.We use method of radioimmunoassay and enzyme linked immunosorbent assay to measure TNF-α、Leptin,APN and Resistin in serum separately.As to mRNA of GLUT-4 in skeletal muscle and resistin in white fat tissue,we use RT-PCR method.From the data we obtain, we may tell American Ginseng can ameliorate IR from both lipocyte cytokine angle and gene expression angle.
At last,we draw the conclusions as follows from the research project.The first one is the IR model in rats were successfully made by high fat diet combined with injecting small dose STZ.The second one is that American Ginseng has the good effects on glycometabolism and lipometabolism,and the active site is 30 percent alcohol elution fraction,60 percent alcohol elution fraction.The third one is American Ginseng is available of ameliorating IR by affecting TNF-α、Leptin、APN and Resistin.The last one is that American Ginseng can also ameliorate IR by boosting up mRNA expression of GLUT-4 and lowering mRNA expression.
引文
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