糖脂平对高脂诱导胰岛素抵抗大鼠脂肪因子与蛋白激酶B的影响

【作者】 林长青；

【导师】 高彦彬；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2009， 博士

【摘要】 本论文共分为两个部分:胰岛素抵抗的文献综述和中药糖脂平干预胰岛素抵抗的实验研究部分。1文献研究本论文文献综述分两个部分,即中医文献研究和现代医学研究进展两部分。中医文献从中医对胰岛素抵抗的病因病机和辩证分型以及临床治疗与实验研究等方面,进行了系统的评述;现代医学综述研究系统回顾了近十几年来国内外对胰岛素抵抗的发病机制以及药物治疗进展方面的进展情况进行了系统的总结和综述。2实验研究目的本研究在糖脂平干预糖耐量低减(IGT),改善胰岛素抵抗疗效确切的基础上,采用细胞分子生物学技术,探讨糖脂平对脂肪细胞因子(脂联素、肿瘤坏死因子)及胰岛素受体传导通路中蛋白激酶B(PKB/Akt)基因表达的影响,阐明糖脂平改善胰岛素抵抗的作用靶点和途径,为中医药改善胰岛素抵抗提供科学依据。方法采用高脂喂养的方法建立诱发胰岛素抵抗大鼠模型。将符合条件的SD大鼠随机分为4组(正常组、模型组、糖脂平组、罗格列酮组),每组10只。中药组给予糖脂平10ml/kg/d(生药20g/kg/d)灌胃;西药组给予文迪亚0.8mg/kg/d灌胃8周;采用胰岛素抵抗评价“金标准”正常葡萄糖钳夹技术,评价糖脂平对胰岛素抵抗大鼠胰岛素敏感性及糖脂代谢的影响;采用RT-PCR技术观察了糖脂平对胰岛素抵抗大鼠脂肪细胞因子(脂联素、肿瘤坏死因子)及胰岛素受体传导通路中蛋白激酶B(PKB/Akt)基因表达的影响。结果1高脂诱导的大鼠模型,与正常对照组比较具有体重增加、血糖升高、空腹胰岛素升高、脂代谢紊乱、葡萄糖输注率(GIR)显著降低等特征,表现出明显的胰岛素抵抗,符合人类胰岛素抵抗的发病特点,是比较理想的胰岛素抵抗动物模型。2糖脂平与罗格列酮均可升高葡萄糖输注率(GIR)M值(P＜0.05、P＜0.01),均可降低空腹血糖、空腹胰岛素、降低TC、LDL-C(P＜0.05),可降低胰岛素抵抗模型大鼠体重(P＜0.05)。3高脂诱导的大鼠模型组与正常对照组比较,附睾脂肪组织脂联素mRNA表达显著降低(P＜0.01),糖脂平与罗格列酮均可上调高脂诱导的大鼠附睾脂肪组织脂联素mRNA表达(P＜0.05、P＜0.01)。4高脂诱导的大鼠模型组与正常对照组比较,附睾脂肪组织肿瘤坏死因子mRNA表达显著增强(P＜0.05),糖脂平与罗格列酮均可下调高脂诱导的大鼠附睾脂肪组织肿瘤坏死因子mRNA表达(P＜0.05、P＜0.01)。5高脂诱导的大鼠模型组与正常对照组比较,附睾脂肪组织与骨骼肌组织蛋白激酶B mRNA表达显著降低(P＜0.05),糖脂平与罗格列酮均可明显上调附睾脂肪这种和骨骼肌组织蛋白激酶B mRNA表达(P＜0.05)。结论糖脂平可降低胰岛素抵抗模型大鼠葡萄糖输注率(GIR)M值,改善胰岛素抵抗;降低胰岛素抵抗模型大鼠体重、改善糖脂代谢紊乱;可上调胰岛素抵抗模型大鼠脂肪组织脂联素mRNA基因表达;下调胰岛素抵抗模型大鼠脂肪组织肿瘤坏死因子基因表达;可上调胰岛素抵抗模型大鼠脂肪组织及骨骼肌组织蛋白激酶B mRNA基因表达。糖脂平可能通过影响脂肪组织的脂联素、肿瘤坏死因子及脂肪与肌肉组织蛋白激酶B基因表达,而发挥改善胰岛素抵抗的作用。更多还原

【Abstract】 There are two parts in this thesis:Reference review of insulin resistance (IR),and experimental study on the prevention and treatment for IR by Tangzhiping.1 reference reviewThis essay reviewed from the advances of such fields as followed:reference review of Chinese medicine and modern medicine research.We had a systematic discussion from the pathogenesis theory,syndrome differentiation,and clinical and experimental study for IR with Chinese medicine.At the sametime,we reviewed the pathogenesis and progressof drugs for IR in modern medicine systematically.2 experimental studyObjectivesBased on the prevention and treatment for IGT,and improving IR with Tangzhiping, we investigated the influence of Tangzhiping on the gene expression of adiposederived cell factor and insulin signaling pathway in T2DM and IR,in order to supply the basic theory and experimental data for researching the mechanism of action of the function of the adiposity in IR and T2DM and for the mechanism of action of Tangzhiping.MethodsWeused IR rats model by high fat,and divided them randomly into four groups: normal group,model group,rosiglitazone group,TZP groups.Every group included 10 rats;fat forage induced insulin rat were used as animal models.Model group and normal group were intragastric administrated with sterile water;western medicine group were intragastric administrated with rosiglitazone,and TZP groups were intragastric administrated with TZP separately.After treated correspondingly separately for 8 weeks,general condition were observed in all groups, hyper insulin mice uglycemic clamp were used for evaluate IR.All mice werekilled to collect the blood,adipocyte and the muscle.Adiponectin,TNF-α,leptin, PKB/Akt was detected by RT-PCR.Results1.Rats model induced by high fat had elevatory body weight,blood sugar and fasting insulin,and had a characteristics of lipid metabolism disorder,the descending of glucose metabolic rate.So this model is comparatively ideal IR animal model.2.TZP and rosiglitazone could increased glucose infusion rate(M)(P＜0.05、P＜0.01),and could decreased fasting blood glucose and serum insulin、TC、LDL-C (P＜0.05),decreased the body weight of IR model rats. 3.Rats model induced by high fat had elevatory adiponcetin mRNA levels in the epididymis(P＜0.05、P＜0.01),which ramarkable reduce than normal groups. TZP and rosiglitazone could increased adiponcetin mRNA levels in the epididymis (P＜0.05、P＜0.01).4.Rats model induced by high fat had descending TNF mRNA levels in the epididymis(P＜0.05、P＜0.01),which ramarkable reduce than normal groups.TZP and rosiglitazone could decreased TNF mRNA levels in the epididymis(P＜0.05、P＜0.01).5.Rats model induced by high fat had elevatory PKB mRNA levels in the epididymis and skeletal muscle(P＜0.05、P＜0.01),which ramarkable reduce than normal groups.TZP and rosiglitazone could increased leptin mRNA levels in the epididymis and skeletal muscle(P＜0.05、P＜0.01).conclusionTZP could descended glucose infusion rate(M),improving IR;descended the body weight and improved lipid metabolism disorder of IR model rats;increased adiponcetin mRNA levels in the epididymis;decreased TNF mRNA and levels in the epididymis;increased leptin mRNA levels in the epididymis and skeletal muscle. So TZP have a role of improving IR through effecting the expression of adiponcetin、TNF、liptin and PKB.更多还原