糖耐康颗粒干预KKAy小鼠胰岛素抵抗作用机制研究

【作者】 江南；

【导师】 刘铜华；

【作者基本信息】 北京中医药大学 ， 中医内科学， 2007， 硕士

【摘要】 本研究对中药复方糖耐康干预自发性2型糖尿病KKAy小鼠胰岛素抵抗进行初步研究,探讨其可能的作用机制,旨在为临床上2型糖尿病的防治寻找新靶点和新药物。论文主要包括文献综述和实验研究两个部分。文献综述分为“2型糖尿病胰岛素抵抗中医药研究概况”与“2型糖尿病胰岛素抵抗现代医学研究状况”两部分。通过查阅近年来国内外2型糖尿病IR相关文献资料,对目前现代医学和中医学对于2型糖尿病胰岛素抵抗的发病机理、治疗用药、研究方法概况进行了较为系统的总结和综述。实验研究部分:研究目的:观察糖耐康颗粒对自发性2型糖尿病KKAy小鼠胰岛素抵抗的治疗作用,探讨其可能机制。研究方法:选用与人类2型糖尿病发病机制相似的自发性2型糖尿病KKAy小鼠作为动物模型,应用糖耐康颗粒对其进行干预,将KKAy小鼠分为模型对照组、糖耐康高、低剂量组及阳性药吡格列酮对照组,并选C57bl/6J小鼠作为阴性对照,观察药物对自发性2型糖尿病KKAy小鼠糖脂代谢、胰岛素敏感性、胰腺、肾脏病理形态学、肿瘤坏死因子(TNF)-α水平、游离脂肪酸(FFA)水平和肾脏ICAM-1表达的影响。研究结果:糖耐康颗粒可明显降低KKAy小鼠的空腹血糖、空腹血清胰岛素以及TNF-α水平,提高胰岛素抵抗指数。糖耐康颗粒有降低血脂、FFA的趋势,可能与治疗时间短有关,其机理有待进一步探索。胰腺组织HE染色结果显示,糖耐康颗粒治疗后减轻了胰岛内B细胞颗粒脱失、空泡变性的程度,B细胞大小、形态维持较好,数目较多。肾脏组织HE染色结果显示:糖耐康颗粒治疗后肾小球系膜内结节状玻璃样物质沉积、肾小管上皮细胞空泡样变性、炎性细胞浸润均有不同程度的改观。肾脏ICAM-1的表达情况:糖耐康颗粒可明显降低KKAy小鼠肾脏组织中ICAM-1的表达。结论:结果表明(1)糖耐康颗粒能够有效改善自发性2型糖尿病KKAy小鼠胰岛素抵抗状态,并能在一定程度上延缓B细胞的衰竭,起到保护作用。推测其机制可能是通过作用于受体后环节,调控TNF-α及游离脂肪酸的水平而起作用。(2)糖耐康颗粒在改善KKAy小鼠胰岛素抵抗的同时,也能有效阻止血管病变的发生和发展,起到保护肾功能、延缓DN发展的作用,但是糖耐康颗粒降低ICAM-1表达具体作用途径仍有待进一步研究。更多还原

【Abstract】 In this study, we use Chinese herbs Tang Nai Kang to intervent IR c-onducting of KKAy diabetic mice, discuss the possible mechanism and w-ant to find new targets and new drugs to prevent type 2 diabetes.This paper includes two parts: review and experimental study.Review includes: " TCM research Overview of insulin resistance in ty-pe 2 diabetes " and " modern medicine research Overview of insulin resi-stance in type 2 diabetes".All recent relevant literature of type 2 diabetes IR research are docu-mented, we summarise pathogenesis, therapeutic medication, research meth-ods of type 2 diabetes IR in modern medicine and TCM . We discuss fu-rtherly the pathogenesis of type 2 diabetes IR in TCM.Study : Objective:To observe the effects of Tang Nai Kang in KKAy diabetic mice.Methods : KKAy diabetic mice were fed with high calorie di-et divided into control group, Tang Nai Kang high dose group, Tang Nai Kang low dose group and positive drug pioglitazone control group. C57bl/6J mice as a negative control. After 8 weeks,glucose and lipid metabolism, the insulin sensitivity, pathomorphology of pancreas and kidney ,tumor ne-crosis factor (TNF) -αlevels, free fatty acid (FFA) levels and renal expre-ssion of ICAM-1 were observed.Results : After eight weeks treatment withTang Nai Kang, FPG, Fins levels, ISI and TNF-αwere significantly chang-ed. Blood Fat and FFA were decreasing, the reason may be short on time, the mechanism yet to be further explored. HE pancreastic tissue staining s-howed that Tang Nai Kang can effectively reduce the degree of B cell de-pletion particles and vacuolation, keep the cell shape.Kidney HE staining r-evealed: After 8 weeks’treatment of Tang Nai Kang, the tubular membranenodular-glass-like material deposition, tubularepithelial cells in vacuolar de-generation, inflammatory cell infiltration in KKAy diabetic mice have varyi-ng degrees of improvement. ICAM-1 expression in renal:Tang Nai Kang ca-n obviously reduce the expression of ICAM-1 in KKAy diabetic mice’s ren-al.Conclusion : The results show (1) Tang Nai Kang can effectively contr-ol insulin resistance in KKAy mice and delay the failure of B cells.The m-echanism may regulate the level of TNF-αand FFA. (2) Tang Nai Kang c-an prevent the occurrence and development of vascular lesions,protect renal function,and delay the development of DN in KKAy diabetic mice.But ho-w can Tang Nai Kang reduce the expression of ICAM-1 remains to be further studied.更多还原