【摘要】：1目的觀察益氣養(yǎng)陰活血方對(duì)早期糖尿病視網(wǎng)膜病變(DR)患者視網(wǎng)膜中央動(dòng)脈(CRA)的血流動(dòng)力性和眼底病變、缺氧誘導(dǎo)因子-1a(HIF-1a)、及血管內(nèi)皮生長(zhǎng)因子(VEGF)等指標(biāo)的影響。并通過(guò)動(dòng)物實(shí)驗(yàn),從分子學(xué)角度探討益氣養(yǎng)陰活血方對(duì)DR的保護(hù)機(jī)理,為臨床上中醫(yī)藥防治DR提供豐富的經(jīng)驗(yàn)和理論依據(jù)。2方法2.1臨床研究選取64例診斷為早期DR的患者,按隨機(jī)數(shù)字表法隨機(jī)分為對(duì)照組和治療組各32例(64只眼),所有患者接受糖尿病教育、采取糖尿病飲食、體育鍛煉、口服降糖藥或胰島素注射等基礎(chǔ)治療。對(duì)照組服用羥苯磺酸鈣膠囊,治療組在對(duì)照組基礎(chǔ)上加用有益氣養(yǎng)陰活血之效的丹蛭降糖膠囊。兩組患者在治療前后均行CRA血流動(dòng)力學(xué)相關(guān)指標(biāo)檢測(cè)、眼底和視力檢查、中醫(yī)癥狀評(píng)分、及血糖、糖化血紅蛋白、血脂、缺氧誘導(dǎo)因子-1a(HIF-1a)、血管內(nèi)皮生長(zhǎng)因子(VEGF)等指標(biāo)的檢測(cè)。兩組治療時(shí)間均為3個(gè)月。2.2動(dòng)物實(shí)驗(yàn)將70只SD大鼠按體重隨機(jī)分組,選取10只大鼠作為空白組,實(shí)驗(yàn)全過(guò)程都喂食普通飼料,另外60只大鼠以高脂飼料喂養(yǎng)+小劑量鏈脲佐菌素(STZ)腹腔注射,造模成功的DM大鼠喂養(yǎng)10周后,分為中藥高、中、低劑量組及模型組,連續(xù)給藥12周。觀察大鼠的一般情況、血糖、血脂及視網(wǎng)膜組織HIF-1a、VEGF、VEGFR2表達(dá)情況。3結(jié)果3.1臨床研究結(jié)果(1)治療后,兩組視網(wǎng)膜中央動(dòng)脈的PSV、EDV、Vm較治療前均有顯著提高(P0.01),PI、RI較治療前均顯著降低(P0.01),治療組治療后各項(xiàng)指標(biāo)和對(duì)照組比較有顯著差異(P0.01)。(2)治療3個(gè)月后,兩組血清VEGF、HIF-1α水平均低于治療前,差異有統(tǒng)計(jì)學(xué)意義(P0.01);治療后治療組血清VEGF、HIF-1α水平下降優(yōu)于對(duì)照組,有明顯差異(P0.01)。(3)治療3個(gè)月后,兩組FPG、2h PG、Hb A1、TG均顯著下降(P0.01),與對(duì)照組比較,治療組FPG、2h PG、Hb A1有顯著差異(P0.01);兩組BMI、TC與治療前比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。(4)治療3個(gè)月后,與對(duì)照組比較,治療組能顯著改善患者的臨床癥狀體征,療效顯著優(yōu)于對(duì)照組(P0.01)。(5)治療組的總有效率為81.67%,對(duì)照組總有效率為65.0%;兩組患者的視力、眼底癥狀均有改善,且治療組視力積分和對(duì)照組相比有顯著差異(P0.01),眼底癥狀積分和對(duì)照組相比有明顯差異(P0.05)。(6)治療期間,兩組患者的肝功能、腎功能及心電圖均未發(fā)現(xiàn)異常,未見(jiàn)過(guò)敏反應(yīng)。3.2動(dòng)物實(shí)驗(yàn)結(jié)果(1)對(duì)DR大鼠的一般情況、體重影響空白組大鼠在整個(gè)實(shí)驗(yàn)期間活躍好動(dòng),精神狀態(tài)良好,每日進(jìn)食進(jìn)水量適中,隨著實(shí)驗(yàn)的進(jìn)行,空白組大鼠的體重持續(xù)增長(zhǎng)。中藥高、中、低劑量組及模型組大鼠的體重均明顯低于空白組,增長(zhǎng)緩慢,且隨著病程進(jìn)展體重增長(zhǎng)趨勢(shì)下降。DM模型大鼠造模成功1周后即開(kāi)始出現(xiàn)多飲多食多尿癥狀,自發(fā)活動(dòng)減少,毛發(fā)缺少光澤,精神萎靡;實(shí)驗(yàn)結(jié)束后,中藥高、中、低劑量組DR大鼠狀態(tài)較模型組好。(2)對(duì)DR大鼠的血糖影響造模成功后,對(duì)比空白組大鼠空腹血糖,中藥高、中、低劑量組及模型組大鼠空腹血糖明顯升高(P0.01);中藥高、中、低劑量組治療12周后,都明顯降低血糖,與模型組比較有顯著差異(P0.01),且中藥高、中劑量組大鼠空腹血糖明顯低于低劑量組,差異有統(tǒng)計(jì)學(xué)意義(P0.01),中藥高、中劑量組大鼠血糖比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)(3)對(duì)DR大鼠視網(wǎng)膜組織VEGF和VEGFR2 m RNA表達(dá)影響與空白組對(duì)比,模型組大鼠視網(wǎng)膜中VEGF,VEGFR2 m RNA含量均明顯增高;治療后中藥高中低各劑量組VEGF,VEGFR2 m RNA表達(dá)水平均較模型組明顯下降(P0.01);較低劑量組,中藥高、中劑量組VEGF、VEGFR2的表達(dá)下調(diào)更為明顯(P0.01)。(4)對(duì)DR大鼠視網(wǎng)膜組織HIF-1a,VEGF,VEGFR2蛋白表達(dá)影響空白組大鼠視網(wǎng)膜組織HIF-1a,VEGF與VEGFR2蛋白的表達(dá)明顯低于模型組(P0.01);中藥高、中、低劑量組HIF-1a,VEGF,VEGFR2蛋白表達(dá)水平較模型組均明顯下降(P0.01);中藥高、中劑量組三種蛋白表達(dá)下調(diào)較低劑量更為明顯(P0.01),中藥高、中劑量組的VEGF、VEGFR2蛋白表達(dá)量未見(jiàn)明顯差異。4結(jié)論益氣養(yǎng)陰活血方可改善DR患者視網(wǎng)膜中央動(dòng)脈血流動(dòng)力性,改善視網(wǎng)膜微循環(huán)障礙,改善視力和眼底視網(wǎng)膜病變,有效改善中醫(yī)癥狀體征,降低患者血糖、血脂,且臨床使用安全有效,并能有效下調(diào)HIF-1a/VEGF/VEGFR2表達(dá),對(duì)HIF-1a/VEGF/VEGFR2具有一定的調(diào)控作用,改善內(nèi)皮細(xì)胞功能障礙,減輕糖尿病視網(wǎng)膜損害,延緩病情進(jìn)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.
【學(xué)位授予單位】：安徽中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R259;R276.7

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2 黃鈺惠;視網(wǎng)膜中央動(dòng)脈血流動(dòng)力學(xué)及血脂改變與早期糖尿病視網(wǎng)膜病變的相關(guān)性研究[D];大連醫(yī)科大學(xué);2014年

3 白晶晶;糖尿病視網(wǎng)膜病變視網(wǎng)膜中央動(dòng)脈血流動(dòng)力學(xué)變化[D];大連醫(yī)科大學(xué);2010年

4 徐淑賢;甲狀腺相關(guān)性眼病治療前后血流動(dòng)力學(xué)分析[D];中南大學(xué);2013年

5 宋璐;阻塞性睡眠呼吸暫停低通氣綜合征患者眼血流的變化[D];山西醫(yī)科大學(xué);2011年

6 張伊;糖尿病患者眼底微循環(huán)病變基礎(chǔ)及其檢查方法的研究探討[D];河北醫(yī)科大學(xué);2009年

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