益气养阴活血法对早期DR视网膜中央动脉血流动力性及血管损伤改变探究

发布时间：2018-10-26 13:04

【摘要】：1目的观察益气养阴活血方对早期糖尿病视网膜病变(DR)患者视网膜中央动脉(CRA)的血流动力性和眼底病变、缺氧诱导因子-1a(HIF-1a)、及血管内皮生长因子(VEGF)等指标的影响。并通过动物实验,从分子学角度探讨益气养阴活血方对DR的保护机理,为临床上中医药防治DR提供丰富的经验和理论依据。2方法2.1临床研究选取64例诊断为早期DR的患者,按随机数字表法随机分为对照组和治疗组各32例(64只眼),所有患者接受糖尿病教育、采取糖尿病饮食、体育锻炼、口服降糖药或胰岛素注射等基础治疗。对照组服用羟苯磺酸钙胶囊,治疗组在对照组基础上加用有益气养阴活血之效的丹蛭降糖胶囊。两组患者在治疗前后均行CRA血流动力学相关指标检测、眼底和视力检查、中医症状评分、及血糖、糖化血红蛋白、血脂、缺氧诱导因子-1a(HIF-1a)、血管内皮生长因子(VEGF)等指标的检测。两组治疗时间均为3个月。2.2动物实验将70只SD大鼠按体重随机分组,选取10只大鼠作为空白组,实验全过程都喂食普通饲料,另外60只大鼠以高脂饲料喂养+小剂量链脲佐菌素(STZ)腹腔注射,造模成功的DM大鼠喂养10周后,分为中药高、中、低剂量组及模型组,连续给药12周。观察大鼠的一般情况、血糖、血脂及视网膜组织HIF-1a、VEGF、VEGFR2表达情况。3结果3.1临床研究结果(1)治疗后,两组视网膜中央动脉的PSV、EDV、Vm较治疗前均有显著提高(P0.01),PI、RI较治疗前均显著降低(P0.01),治疗组治疗后各项指标和对照组比较有显著差异(P0.01)。(2)治疗3个月后,两组血清VEGF、HIF-1α水平均低于治疗前,差异有统计学意义(P0.01);治疗后治疗组血清VEGF、HIF-1α水平下降优于对照组,有明显差异(P0.01)。(3)治疗3个月后,两组FPG、2h PG、Hb A1、TG均显著下降(P0.01),与对照组比较,治疗组FPG、2h PG、Hb A1有显著差异(P0.01);两组BMI、TC与治疗前比较,差异无统计学意义(P0.05)。(4)治疗3个月后,与对照组比较,治疗组能显著改善患者的临床症状体征,疗效显著优于对照组(P0.01)。(5)治疗组的总有效率为81.67%,对照组总有效率为65.0%;两组患者的视力、眼底症状均有改善,且治疗组视力积分和对照组相比有显著差异(P0.01),眼底症状积分和对照组相比有明显差异(P0.05)。(6)治疗期间,两组患者的肝功能、肾功能及心电图均未发现异常,未见过敏反应。3.2动物实验结果(1)对DR大鼠的一般情况、体重影响空白组大鼠在整个实验期间活跃好动,精神状态良好,每日进食进水量适中,随着实验的进行,空白组大鼠的体重持续增长。中药高、中、低剂量组及模型组大鼠的体重均明显低于空白组,增长缓慢,且随着病程进展体重增长趋势下降。DM模型大鼠造模成功1周后即开始出现多饮多食多尿症状,自发活动减少,毛发缺少光泽,精神萎靡;实验结束后,中药高、中、低剂量组DR大鼠状态较模型组好。(2)对DR大鼠的血糖影响造模成功后,对比空白组大鼠空腹血糖,中药高、中、低剂量组及模型组大鼠空腹血糖明显升高(P0.01);中药高、中、低剂量组治疗12周后,都明显降低血糖,与模型组比较有显著差异(P0.01),且中药高、中剂量组大鼠空腹血糖明显低于低剂量组,差异有统计学意义(P0.01),中药高、中剂量组大鼠血糖比较,差异无统计学意义(P0.05)(3)对DR大鼠视网膜组织VEGF和VEGFR2 m RNA表达影响与空白组对比,模型组大鼠视网膜中VEGF,VEGFR2 m RNA含量均明显增高;治疗后中药高中低各剂量组VEGF,VEGFR2 m RNA表达水平均较模型组明显下降(P0.01);较低剂量组,中药高、中剂量组VEGF、VEGFR2的表达下调更为明显(P0.01)。(4)对DR大鼠视网膜组织HIF-1a,VEGF,VEGFR2蛋白表达影响空白组大鼠视网膜组织HIF-1a,VEGF与VEGFR2蛋白的表达明显低于模型组(P0.01);中药高、中、低剂量组HIF-1a,VEGF,VEGFR2蛋白表达水平较模型组均明显下降(P0.01);中药高、中剂量组三种蛋白表达下调较低剂量更为明显(P0.01),中药高、中剂量组的VEGF、VEGFR2蛋白表达量未见明显差异。4结论益气养阴活血方可改善DR患者视网膜中央动脉血流动力性,改善视网膜微循环障碍,改善视力和眼底视网膜病变,有效改善中医症状体征,降低患者血糖、血脂,且临床使用安全有效,并能有效下调HIF-1a/VEGF/VEGFR2表达,对HIF-1a/VEGF/VEGFR2具有一定的调控作用,改善内皮细胞功能障碍,减轻糖尿病视网膜损害,延缓病情进展。
[Abstract]:Objective To observe the effects of Yiqiyangyin Huoxue Recipe on the hemodynamics and fundus lesion, hypoxia inducible factor-1a (hypoxia-1a) and vascular endothelial growth factor (VEGF) in patients with early diabetic retinopathy (DR). and through animal experiments, the protective mechanism of benefiting qi and nourishing yin and promoting blood circulation is researched from molecular science to provide rich experience and theoretical basis for the clinical traditional Chinese medicine prevention and treatment DR. 64 patients diagnosed as early DR are selected according to the clinical study. According to the random number table method, 32 cases (64 eyes) were randomly divided into control group and treatment group (64 eyes). All patients were treated with diabetes education, diabetic diet, physical exercise, oral hypoglycemic or insulin injection. The control group took the calcium hydroxybenzene sulfonate capsule, and the treatment group had the effect of benefiting qi, nourishing yin and promoting blood circulation on the basis of the control group. Before and after treatment, two groups of patients were tested for blood flow dynamics related index, fundus and vision examination, TCM symptom score, and blood glucose, glycosylated hemoglobin, blood lipid, hypoxia inducible factor-1a (TUNEL-1a), vascular endothelial growth factor (VEGF), and so on. In the two groups, 70 SD rats were randomly grouped according to body weight, 10 rats were selected as blank group, the whole process was fed with normal feed, and 60 rats were fed with high fat feed + low dose chain trizocin (STZ) for intraperitoneal injection. After 10 weeks of feeding, DM rats were divided into three groups: Chinese medicine, middle and low dose groups and model group. In general, the expression of blood glucose, blood lipid and retinal tissue-1a, VEGF and VEGFR2 were observed in rats. The results of 3. 1 Clinical study (1) showed significant improvement (P0.01), PI, RI decreased significantly before treatment (P0.01), and there was significant difference between the indexes after treatment and control group (P0.01). (2) After 3 months of treatment, the levels of VEGF and p27-1 in the two groups were significantly lower than those of the control group (P <0.01). (3) After 3 months of treatment, both groups of FPG, 2h PG, Hb A1 and TG decreased significantly (P0.01). Compared with the control group, there was significant difference in FPG, 2h PG and Hb A1 (P0.01). (4) After 3 months of treatment, compared with the control group, the treatment group can significantly improve the clinical symptoms and signs of the patients, and the curative effect is better than that of the control group (P0.01). (5) The total effective rate of the treatment group was 81.67%, the total effective rate of the control group was 65.0%, the visual acuity and eyeground symptom of the two groups were improved, and there was a significant difference between the vision score of the treatment group and the control group (P0.05). (6) During the treatment, the liver function, renal function and electrocardiogram of the two groups were not found abnormal, and no allergic reaction was found. The daily intake was moderate, and as the experiment progressed, the body weight of the blank group continued to grow. The body weight of rats with high, middle, low dose and model group was significantly lower than that in blank group, the growth was slow, and the trend of body weight gain decreased with the progression of disease. In DM model rats, polyuria and polyuria began to occur after 1 week, spontaneous activity decreased, the hair lacked luster, and the spirit was listless; after the experiment, the state of DR rats was better than that in low dose group. (2) After the successful model of blood sugar in DR rats, fasting blood glucose and Chinese medicine were significantly increased compared with those in blank group (P <0.01). Compared with the model group (P0.01), the fasting blood glucose of the Chinese traditional Chinese medicine was significantly lower than that of the low-dose group (P <0.01), the difference was statistically significant (P <0.01), the traditional Chinese medicine was high, and the blood sugar in the middle-dose group was compared with that in the middle-dose group. The expression of VEGF and VEGFR2 mRNA in retina of DR rats was significantly higher than that in blank group (P <0.05) (P <0.05) (P <0.05) (P <0.05) (P <0.05) (P <0.05). The expression level of VEGFR2 mRNA was significantly lower than that in the model group (P0.01); the expression of VEGF and VEGFR2 in the lower dose group and the medium dose group were significantly lower than that in the lower dose group (P0.01). (4) The expression of VEGF and VEGFR2 protein in retina tissues of DR rats was significantly lower than that in the model group (P0.01). The expression of VEGF and VEGFR2 protein in Chinese medicine was higher than that of Chinese medicine (P0.01). The expression of VEGF and VEGFR2 protein in Chinese medicine was higher than that in the middle dose group (P0.01). improve that microcirculation disturbance of the retina, improve the vision and fundus retinopathy, effectively improve the symptom sign of the traditional Chinese medicine, reduce the blood sugar and blood fat of the patient, and can effectively regulate the expression of the vascular endothelial cell-1a/ VEGF/ VEGFR2, have a certain regulation effect on the anti-inflammatory factor-1a/ VEGF/ VEGFR2, and improve the dysfunction of endothelial cells, Relieve diabetic retinopathy and delay progression of the disease.
【学位授予单位】：安徽中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R259;R276.7

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