【作者】 王小川；

【导师】 余杨桂；

【作者基本信息】 广州中医药大学 ， 中西医结合临床， 2005， 博士

【摘要】 糖尿病(Diabetes mellitus,DM)是严重威胁人类健康和生命的常见疾病,发病率逐年增长,随病程进展出现糖尿病微血管并发症,并累及全身各个系统。糖尿病视网膜病变(Diabetic retinopathy,DR)是其主要且严重的微血管病变之一。属中医“消渴目病”范畴,病因复杂,病程长,并发症多,致盲率高。目前对于DR的发病机理及治疗方法尚未取得突破性的进展。西医对DR的治疗原则是:单纯期内科治疗、眼科定期观察;增殖期行全视网膜光凝固术,严重的增殖期病变则需进行玻璃体切割术。对于早期DR尚无一种疗效理想的防治药物,中医药经过长期的临床观察,显示对早期DR有一定的疗效,如促进患者视力的提高及眼底出血、渗出、水肿的吸收,且大多数患者经过服用中药后,全身症状改善,但大多数为临床病例报告,缺乏严密对照观察,极少实验动物对中药药效研究。严格控制血糖对治疗DR有益,但并不能完全阻止其发生发展。西药导升明、递法明、弥可保等亦可用于早期DR治疗,但价格昂贵、疗效亦不满意。激光对增殖前期、增殖期DR是一种有效的治疗方法,但会出现如光凝斑扩大、视网膜下新生血管、视野缺损等并发症。基于DR发病率高及治疗现状不理想,目前研究的切入点为早期预防、早期治疗,防止疾病进入晚期。 本研究在前期工作中根据导师余杨桂教授多年的临床实践,组成以益气养阴健脾、化瘀通络为治法的滋肾健脾化瘀方(原名糖网宁),通过长期的临床观察及实验证明:本方联合激光治疗DR增殖前期及增殖期,网膜水肿、出血及渗出均有不同程度吸收,新生血管萎缩退化或缩小。视功能改善,全身症状好转。同时通过实验发现,本方能改善实验DM大鼠视网膜毛细血管超微结构损害。 本研究拟用滋肾健脾化瘀方进行针对DR早期的阳性药对照的临床观察,评价其有效性,并通过眼底局部病变与视力、血糖、血脂、中医证候的积分关系来阐明全身调控及眼局部病变改善的关系。 实验方面,对DR发病机理的研究目前大多集中于视网膜毛细血管病变上,而对视网膜神经组织病变方面涉及较少。本研究通过建立链脲佐菌素(Streptozotocin,STZ)诱导的SD大鼠DM模型,并用滋肾健脾化瘀方和导升明对照治疗,观察消化酶铺片及透射电镜下视网膜神经组织及血管组织的改变,探讨并明确DR发病的视网膜血管和神经机制,从而寻找安全有效的神经网膜及视网膜血管保护方法,为探索对DR具有保护作用的中药多途径、多靶点作用机理提供一定的实验依据。 第一部分 文献研究 通过对中医和西医学有关DR的病因病机、发病机理及治疗的研究现状综述,认识到DR早期以气阴两虚证居多,治则主要是益气养阴、活血通络为主。西医学认为DR发病与全身关系密切,也与眼局部因素有关,发病机理多样,治疗方法也多样,更多还原

【Abstract】 Diabetes mellitus is the common disease which severely threaten the human’ s health and life. The incidence rate increases every year and then the capillary vessel complication occurred. Diabetic retinopathy is one of the server complication. It belongs to "Xiaokemubing" of traditional Chinese medicine. The blindness ratio is hign. There don’ t take Break-through progress in DR’ s episode and therapeutics at present. The western medicine therapeutic principle about DR is: nonproliferative phase Internal medicine and have a regular Observation of eyes; proliferative phase rrp, some countries and areas recommend to take Doxim, Severe proliferative diabetic retinopathy need vitrectomy. There have no ideal medicine which can prevent or cure DR, the traditional Chinese medicine can elevate the patients’ visual and absorb the hemorrhage hard exudation edema of fundus. After taken the Chinese drug, the patients’ symptoms by systems improving, but the most are case reports, not use the case control and lack of drug efficacy study about experimental animal. It’ s beneficial control the blood sugar, but it can not prevent DR’ s occurrence and development. The Western medicine Doxium Difrarel Methycobal use for DR, but the price are expensive, therapeutic effect disaffect. Laser is an effective method for pre-proliferative DR or PDR, it also have many complications. So the emphasis is early treatment and early prevention.This research is based on Professor Yuyanggui’ s clinical practice, use the Zishenjianpihuayufang which can supplementing qi and nourishing yin disperse blood stasis and dredge collateral. The clinic and experiment results proved that laser with this medicine can cure PDR and pre-PDR, this can degenerate the new vessels and absorb the hemorrhage hard exudation edemaof fundus. The experiment discovered that it can improve the DM rats’ bloodcapillary’ s ultramicrostructure lesion of retina.This research will use this medicine to cure the pristine DR and evaluate it’ s efficacy and clarity the relationship of system control and local control through the fundus vision blood sugar blood fat traditional Chinese syndrome penthemeron.Until now, the experimental research most concentrate on telangiosis of retina, but less on nerve tissue of retina. There have many electrophysiology indicate that the early phase of DR has the abnormality of VEP, in order to identify the neuromechanism and retinal vessel pathogenety, we use"Zishenjianpihuayufang" and doxium to cure the STZ rats and observed the vascular tissue and nerve tissue’ s change and provide experimental basement on the traditional Chinese medicine’ s mechanism of action.The first part: Literature reviewTo review the mechanism, therapeutics of TCM and western medicine, realize that the type of DR’ s earlier period is QiYinLiangXu, so TCM always use invigorating SHEN, PI, QI, YIN drugs. Western medicine think DR’ s episode is related to general factors, but also to local factors, but don’ t find operative methods. This research analysis the effect of Zishenjianpihuayufang to cure the earlier period of DR and use experiment to find out its therapeutics and observed the vascular tissue and nerve tissue’ s change and provide experimental basement of the traditional Chinese medicine’ s mechanism of action.The second part: The evaluation about Zishenjianpihuayufangto cure early period of DRPurpose: To use this medicine to cure the pristine DR and evaluate it’ s efficacy and clarity the relationship of system control and local control through the fundus vision blood sugar blood fat traditional Chinese syndrome penthemeron.Methods: use random, matched control, simple center methods, patients with earlier period of DR who match with the standards diagnosis of deficiency of qi and yin, the cure cause is three months. The two groups compare withequilibrium. The objective markers includes blood sugar, FFA, ERG, blood lipid , traditional Chinese syndrome penthemeron and so on, observe the therapeutic effect of two drugs. All data were analysed by T test, Crosstab analysis and X2 test, Ridit test, spersman correlation analysis with the soft package of SPSS13. 0. P≤0.05 is significant difference or correlation. Results: The two groups have comparability before treatment. Zishenjianpihuayufang have more significant difference in visual, traditional Chinese syndrome penthemeron., ops amplitude than doixum, but have no significant difference in the pathological changes of fundus. The hard exudation has significant correlation with total cholesterol. Microaneurysm, hemorrhage, macular edema have no significant correlation with total cholesterol. The visual of early phase DR has significant correlation with the severity of macular edema. Conclusion:1. The hard exudation has significant correlation with total cholesterol. The step up of TC will raise the risk of hard exudation of retina. It can have significant meaning for DR to ameliorate TC.The visual of early phase DR has significant correlation with the severity of macular edema. This is the important factor in visual of early phase of DR.2. It can improve the blood circulation of entoretina3. Zishenjianpihuayufang which can supplementing qi and nourishing yin and promoting blood circulation to remove meridian obstruction have significant effect on early phase of DR and have more significant effect in visual, traditional Chinese syndrome penthemeron., ops amplitude than doixum, but have no significant effect in the pathological changes of fundus. Zishenjianpihuayufang can not only ameliorate the pathological changes of fundus, but also ameliorate the quality life of pathiets.The third part: the experimental study about Zishenjianpihuayufang to impact experimental diabetic rats’ retina.Purpose: To discuss the pathological change about the electron microscope of nerve retina, blood vessel of retina, the digestive enzyme stretched preparation of blood vessel of retina after the post-treatment of Zishenjianpihuayufang and discuss the superiority of TCM protecting blood更多还原