【作者】 李泽光；

【导师】 栗德林；

【作者基本信息】 黑龙江中医药大学 ， 中医内科学， 2009， 博士

【摘要】 糖尿病足(Diabetic Foot，简称DF)是糖尿病患者并发于足部的一种损及神经、血管、皮肤、肌腱、骨骼，并常导致肢端坏疽的慢性进行性病变。是糖尿病的严重并发症之一，是非外伤性截肢的主要原因。此病变多发于肢体末端，属于中医学“脱疽”等范畴。近年来发病率呈明显增加趋势，引起了国内外学者普遍重视。本课题根据导师创立的“五脏柔弱，内热熏蒸，伤津耗气，血稠液浓，瘀塞毒壅”的糖尿病足病机新理论，结合其本虚标实的病机特点，针对气阴两虚、瘀塞毒壅的临床表现，提出了益气养阴、通塞解毒的治疗原则，并依法立方组成复方糖足康方，应用于临床，取得较好的疗效。拓展了糖尿病足的治疗理论。目的：通过观察复方糖足康胶囊对家兔糖尿病足模型的炎症因子水平及表达的影响，探讨糖尿病足的发病机制，揭示中药复方治疗糖尿病足的作用机理。方法及结果：根据文献资料成功建立了“家兔糖尿病足”模型；运用生化、光镜、免疫组化等手段和方法，通过检测复方糖足康胶囊对糖尿病足家兔模型CR-P、IL-6、MMP-9等炎症指标和血脂、血糖、胰岛素相关因子水平的影响以及TGF-β1、MMP-9、TβR-Ⅰ表达情况和皮肤血管的形态学病理变化，综合分析其作用机理。结果显示复方糖足康胶囊能够明显降低糖尿病足模型炎症因子的水平及改善相关因子指标。能够调节TGF-β1、MMP-9表达，抑制ECM合成，病理显示对家兔股动脉内膜具有修复作用。结论：DF为本虚标实之证，以气阴两虚为本，瘀塞毒壅为标，益气养阴、通塞解毒治疗之法，切合本病病机特点，体现了中医辨证论治的整体性，通过实验证明是治疗糖尿足的有效治法，复方糖足康胶囊是临床治疗DF的有效良方，本实验为中医治疗糖尿病足提供了新的思路。本研究根据文献资料施加多种因素成功建立家兔糖尿病足模型，该模型制作方法可靠、模型稳定，是供临床研究糖尿病足较理想的动物模型。复方糖足康胶囊对家兔糖尿病足模型具有降糖降脂作用，且明显优于通塞脉片对照组，有效降低家兔糖尿病足模型CRP、IL-6、MMP-9炎症指标的水平，优于通塞脉片对照组(P＜0．05)，组间比较亦具明显差异性(p＜0．05)，从实验角度证明该药疗效确切。经复方糖足康胶囊治疗后家兔血管的TGF-β1的表达增加、MMP-9的表达受到抑制。推测复方糖足康胶囊通过调节TGF-β1、MMP-9的表达，抑制ECM合成，最终抑制和延缓了本病的进展。复方糖足康胶囊对家兔股动脉内膜具有修复作用，对硬化斑块的有抑制作用，且优于通塞脉片对照组(p＜0．05)。治疗组与对照组兔足背皮肤未见明显病理改变。模型组则部分家兔出现表皮溃疡面坏死形成。说明复方糖足康胶囊能有效抑制本病的进一步发展。通过对家兔糖尿病足模型CRP、IL-6、MMP-9炎症指标及相关因子影响的研究，表明炎症因子与糖尿病足的发生、发展呈正相关，与动脉粥样硬化的存在和严重性亦有明显相关性，炎症参与了糖尿病大血管病变的发生发展，验证了炎症学说的成立。因此认为临床上对糖尿病足除了控制血糖外，降低炎症反应，加强抗炎的治疗也应当成为糖尿病足综合治疗的重要部分。以上研究证明复方糖足康胶囊能有效抑制和延缓本病的进一步发展，从而在对糖尿病足的治疗中起着积极的作用。更多还原

【Abstract】 Diabetic foot,as a chronic,progressive disease,is one seriouscomplication of diabetes,which is characterized by the damage of nerves,blood vessels,skins,tendons,skeleton,and usually accompanied bygangrene in terminal ends of limbs.It is also regarded as a major reason ofnon-traumatic amputation.According to the classification of TraditionalChinese Medicine,diabetic foot is a kind of Tuo-gangrene.Due to theincreasing incidence of the disease,greater attention has been paid to theresearch of the disease by the domestic specialists and experts.Based on the new mechanism put forward by Professor Li,the author’tutor,“Malnutrition of the five Zang-organs;interior coagulation of dampheat;consumption of Qi and body fluid;thickness of blood and fluid;obstruction of phlegm”,as well as the attention to the characteristics of thedisease,whose feature is deficient origin and excessive superficiality,considering the clinical expression of deficiency of Qi and Yin,togetherwith obstruction of stasis and accumulation of toxin,this research focusesmainly on the treatment of diabetic foot.As a result of the study,thetreatrnent principles—supplementing Qi and nourishing Yin;relievinginternal heat has been put forward by the author.In addition,TangzukangCompound capsule,as an effective prescription has been found and put intouse.Ideal Treatment effect has been achieved,which may guarantee thewidening of treatment theory of diabetes.Objectives:The purpose of the experiment is to find out the effect ofTangzukang Compound capsule on the contents and expressions ofinflammation factors in model rabbits with diabetic foot.A detaileddiscussion has been conducted concerning the mechanism of diabetic foot,which may lead to the exploration of the treatment mechanism of diabeticfoot by Traditional Chinese Medicine.Methods and results:Successfully establish the model of diabetic footin rabbits according to the literature materials.The methods of biochemistry,light microscope and immunohistochemistry were applied in the experiments.Based on the analysis of the effect of Tangzukang Compound capsule on the inflammation factor level—CR-P、IL-6、MMP-9,and TGF-β1、MMP-9、TβR-Ⅰexpression in diabetic foot model rabbits,it has been proved thatTangzukang Compound capsule may obviously reduce the levels ofinflammation factors,adjust TGF-β1、MMP-9 expression,and inhibit thecomposing of ECM in diabetic foot model rabbits.Tangzukang Compoundcapsule plays a role of repairing on the endomembrane of femoral artery indiabetic foot model rabbits.Conclusions:DF,characterized by deficient origin and excessivesuperficiality,and deficiency of Qi and Yin,can be treated effectively by theapplication of supplementing Qi and nourishing Yin;relieving internal heat.This research supplies practical methods to DF treatment,which representsthe holistic treatment and the thought of Traditional Chinese Medicine.Italso widens the horizon of treatment for diabetes from the perspective ofTraditional Chinese Medicine.After this treatment,the levels ofCR-P、IL-6and MMP-9 in the serum of model rabbits all have been improved,andperformed better compared with the cotroll group(p＜0.05).Adjustment ofthe expression ofTGF-β1、MMP-9 and inhibition of the composing of ECMin diabetic foot model rabbits also displays the fact that TangzukangCompound capsule plays the role of repairing on the endomembrane offemoral artery in diabetic foot model rabbits,and performed better comparedwith the cotroll group(p＜0.05).Inflammation factors and the appearance aswell as development of diabetes are relevant clearly.Therefore,attachmentshould be added in the clinical treatment of diabetes to the reinforcement ofanti-inflammation factors.The analysis above shows that Tangzukang Compound capsule mayeffectively inhibit and postpone the development of the disease;hence it canplay an active role in the treatment of diabetes.更多还原