【作者】 杨清峰；

【导师】 徐云生；

【作者基本信息】 山东中医药大学 ， 中医内科学， 2013， 博士

【摘要】 目的:观察补肾益气活血法对老年2型糖尿病颈动脉硬化及血管内皮功能的影响，并通过实验研究探讨该治法改善血管内皮功能、减轻动脉硬化的机制。方法:1.临床研究选择符合老年2型糖尿病西医诊断标准及中医肾虚血瘀证辨证分型标准，合并有颈动脉粥样斑块形成者61人；随机分对照组（30人）、试验组（31人），对照组予以常规降糖治疗，试验组在此基础上加服补肾益气活血方，治疗8周，观察治疗前后血糖、糖化血红蛋白、中医症候疗效变化，并对血脂、内皮素（ET)和一氧化氮(NO)、血栓素B2(TXB2)和6-酮-前列环素(6-Keto-PGF1α)、颈动脉内膜中层厚度、动脉斑块面积等相关指标进行比较。2.试验研究将WISTAR雄性大鼠随机分为3组，分别为空白组对照组（以下简称空白组）、模型对照组（以下简称模型组）和补肾益气活血方试验组（以下简称试验组），每组各10只。以高脂高糖饲料喂养4周后造模，造模后试验组大鼠灌服补肾益气活血方中药混悬液，连续灌胃6周。6周后观察各组大鼠的体重、血糖、血脂、及ET、N0，TXB2、6-Keto-PGF1α、AGEs、eNOS，并取心肌、主动脉做病理切片进行显微镜下观察。结果:临床研究显示试验组患者各项中医临床症状改善明显，空腹血糖、餐后2小时血糖和糖化血红蛋白均较治疗前降低，试验组治疗后糖化血红蛋白下降较对照组明显；试验组可显著改善患者内皮功能，疗效优于对照组；试验组可明显降低患者甘油三酯、总胆固醇、低密度脂蛋白胆固醇水平，疗效优于对照组；试验组在降低颈动脉内膜中层厚度，减少颈动脉斑块面积方面优于对照组。实验研究显示试验组可改善2型糖尿病模型大鼠一般状况，在降糖，调节血脂和调节内皮功能方面均具有明显的作用，镜下病理观察试验组动脉粥样硬化程度较模型组减轻，能进一步降低模型大鼠血AGEs水平，升高eNOS水平。结论:1.本研究结果表明补肾益气活血法有明显的内皮保护和减轻动脉粥样硬化作用，能改善肾虚血瘀型老年2型糖尿病患者的中医临床症状。2.补肾益气活血法改善动脉硬化，改善内皮功能，其作用不仅仅依赖降低血糖，可能通过调节血脂，减少AGEs是生成，调节eNOS活性等多个靶点、多重机制发挥作用。更多还原

【Abstract】 Objective: To observe the influence of the method of Tonifying the kidney,Supplementing Qi and Activating blood circulation on elderly type2diabetic carotidatherosclerosis and endothelial function, we conduct clinical study and experimental studyto discuss the mechanism on this therapeutic method how to improve the vascularendothelial function and reduce atherosclerosis.Method:1. Clinical research: Select61patients of eldly type2diabeticarteriosclerosis which both meet the Western diagnosis standard, and simultaneously meetTCM syndrome type of kidney-deficiency and blood stasis, randomly assigned to thecontrol group (30patients) and the test group (31patients).The control group receivedconventional hypoglycemic therapy, the test group also received conventionalhypoglycemic therapy, but add the Chinese medicine decoction based of the method ofTonifying the kidney, Supplementing Qi and Activating blood circulation in addition. After8weeks of treatment, we observed the change of blood glucose, glycosylated hemoglobin,the efficacy of TCM symptoms before and after treatment, and compared the relevantindicators such as hemorheology, endothelin (ET) and nitric oxide (NO), thromboxane B2(TXB2) and6-Keto-prostacyclin (6-Keto-PGF1α), carotid intima-media thickness andarterial plaque area.Experimental study: Thirty male Wistar rats were randomly divided into3groups, i.e.the blank control group (hereinafter referred to as the blank group), the model controlgroup (hereinafter referred to as the model group) and the experimental group whichreceived the Chinese medicine decoction based of method of Tonifying the kidney,Supplementing Qi and Activating blood circulation (hereinafter referred to as the experimental group), each group had10rats. The latter two groups were fed with the highfat and sugar diet for4weeks to make the experimental modle, After the modeling, theexperimental rats fed with the Chinese medicine decoction based of method of Tonifyingthe kidney, Supplementing Qi and Activating blood circulation for6weeks. After thetreatment, we observed the results including the body weight, blood glucose, blood lipid,and ET, N0,TXB2,6-Keto-PGF1α, AGEs, eNOS of each group, and took the myocardium,aortic pathological sections to observe under the microscope.Results: The clinical study displayed that the TCM clinical symptoms of the patientsof the test group were improved clearly, and their Fasting glucose,2-hour postprandialblood glucose and glycosylated hemoglobin were reduced than before treatment. Aftertreatment, glycosylated hemoglobin declined clearly in the test group compared with thecontrol group control group. The test group significantly improved endothelial function inpatients, clearly reduced triglycerides, total cholesterol, low-density lipoprotein cholesterollevels, reduced carotid intima-media thickness, and reduced arterial plaque area, theeffects are better than the control group.Experimental studies have shown that the experimental group drugs can improve thegeneral condition of the type2diabetic rat models, and have a clear role in hypoglycemic,regulation of blood lipid and regulating endothelial functions. Arteriosclerosis situation ofthe experimental group was significantly reduced compared with the model group fromhistological observation. On the other hand, the experimental group drugs can furtherreduce the model rat serum AGEs content and increase eNOS content.Conclusions:1. The study results show that the method of tonifying the kidney,Supplementing Qi and Activating blood circulation have significant endothelial protectioneffect and can reduce arteriosclerosis, so it can improve the clinical symptoms of thepatients with elderly type2diabetes mellitus which differentiated as kidney-deficiency andblood stasis type.2. The method of tonifying the kidney, Supplementing Qi and Activatingblood circulation can improve arteriosclerosis and enhance endothelial function does notdepend only on lower blood sugar, but also possibly through regulation of blood lipid,reducing the AGEs generating, regulating eNOS activity. These multiple targets, multiplemechanisms play as a role.更多还原