Ang-1、VEGF在早期糖尿病大鼠视网膜中的表达

发布时间：2018-03-14 21:33

本文选题：血管生成素-1　切入点：血管内皮生长因子　出处：《石河子大学》2010年硕士论文　论文类型：学位论文

【摘要】：目的：探讨血管生成素-1(angiopoietin-1, Ang-1)和血管内皮生长因子(vascular endothelial growth factor, VEGF)在早期糖尿病大鼠视网膜中的表达及其意义。方法：制备类似人类I型糖尿病大鼠动物模型,取40只SD雄性大鼠分糖尿病组28只及止常对照组12只,糖尿病组28只SD雄性大鼠腹腔注射STZ60mg.Kg1,建模成功后分别在1周、2周、3周、4周取糖尿病组各7只及正常对照组3只摘取大鼠眼球,应用免疫组化法检测Ang-1、VEGF在视网膜中的表达。结果：Ang-1在1~4周止常对照组大鼠视网膜切片上未见阳性表达,在1~3周糖尿病大鼠视网膜的切片上内界膜、内核层、神经节细胞层及散在血管旁细胞免疫反应阳性呈棕黄色,定位于双极细胞、Muller细胞及血管旁周细胞胞浆,阳性表达并成上升趋势,4周时糖尿病大鼠视网膜中血管间隙增宽,视网膜厚度变薄,但血管形态无明显改变,Amg-1表达阳性率降低,已成阴性表达。Ang-1在糖尿病大鼠视网膜中表达1周阳性率约为70.0%,2周阳性率约为80.0%,3周阳性率约为83.3%,4周阳性率约为22.2%,已为阴性表达。糖尿病组4周之间Ang-1阳性率进行X2检验,X2=21.67,P=0.010(P0.05)有统计学意义,正常组与糖尿病1~3周间Ang-1的表达阳性率统计学分析有显著性差异(P0.01),而与糖尿病4周组无差异(P＞0.05)。VEGF在1~4周正常大鼠对照组切片上视网膜各层均可见阴性染色反应,而在1~4周糖尿病模型组切片上均可见位于视网膜内核层的双极细胞、色素上皮细胞层以及散在的血.管内皮细胞、Muller细胞的染色反应,1~3周出现阳性表达上升趋势,4周表达有所下降,但仍在范围之内。VEGF在糖尿病大鼠视网膜中表达1周阳性率约为75.0%,2周阳性率约为85.9%,3周阳性率约为90.0%,4周阳性率约为73.2%。在部分切片的内界膜亦可见浅棕色弱阳性反应；4周时可见毛细血管间隙增宽。糖尿病组4周之间VEGF阳性率进行X2检验,X2=14.45,P0.05。正常对照组与糖尿病各组问VEGF的表达阳性率进行统计学分析有差异P0.05。结论:1、糖尿病大鼠4周时视网膜已出现明显改变：视网膜厚度变薄,血管壁间隙增宽,未见血管旁细胞。2、Ang-1、VEGF在早期糖尿病大鼠视网膜中1~3周出现高表达,4周时表达下降,且二者出现分离现象,推测随着病程的延长,血管通透性随着增加,Ang-1表达会越来越少,而VEGF表达会越来越多。3、Ang-1作为抗渗透因子,VEGF为渗透因子,在血管完整性中起着重要的作用,二者失去平衡后,即出现血管渗透,从而产生刺激血管新生的因子释放。由此明确了Ang-1在早期糖尿病视网膜中的表达,可作为以后糖尿病视网膜病变早期干预治疗指南措施之一。
[Abstract]:Aim: to investigate the expression and significance of angiopoietin-1 (Ang-1) and vascular endothelial growth factor (VEGF) in retina of early diabetic rats. Methods: animal models similar to human type I diabetes were established. Forty SD male rats were divided into diabetic group (n = 28) and control group (n = 12). Twenty-eight male SD rats in the diabetic group were injected intraperitoneally with STZ60 mg 路Kg1.After the model was successfully established, 7 rats in the diabetic group and 3 rats in the control group were enucleated at 1 week, 2 weeks, 3 weeks and 4 weeks, respectively. The expression of Ang-1VEGF in the retina was detected by immunohistochemical method. Results there was no positive expression of VAng-1 on the retinal sections of the control group from 1 to 4 weeks, but the immunoreactivity of the upper inner boundary membrane, the nuclear layer, the ganglion cell layer and the paravascular cells in the retina slices of the diabetic rats at the 1st and 3rd week were brown and yellow. The positive expression of amg-1 was observed in the cytoplasm of the Muller cells and perivascular cells located in the bipolar cells. The positive expression of Amg-1 in the retina of diabetic rats increased after 4 weeks, but the positive rate of Amg-1 expression was decreased, but the retinal thickness became thinner, but there was no obvious change in the morphology of the blood vessels, but the positive rate of Amg-1 expression was decreased. The positive rate of negative expression of Ang-1 in the retina of diabetic rats was 70.0and the positive rate was about 80.03 weeks after 2 weeks. The positive rate of positive expression of Ang-1 in the retina of diabetic rats was about 83.3 and 22.2.The positive rate of Ang-1 in the diabetic group was determined by X2 between 4 weeks and 4 weeks. There was statistical significance in the test of X2 (21.67) and P0. 010 (P0. 05). There was significant difference in the positive rate of Ang-1 expression between the normal group and the diabetic group within 3 weeks, but there was no significant difference between the normal group and the 4 week diabetic group (P > 0.05). Negative staining was observed in all layers of the retina of the normal control group at the 1st and 4th week. However, bipolar cells located in the nuclear layer of the retina were found on the slices of the 1-week diabetic model group. The staining reaction of pigment epithelial cells and scattered blood. The positive expression of Muller cells increased in the 1st week and decreased in the 4th week. However, the positive rate of VEGF expression in the retina of diabetic rats was 75.0 in 1 week and 85.9 in 2 weeks. The positive rate was 90.0 in 4 weeks and 73.2 percent in 4 weeks. The light brown weak positive reaction was also found in the inner limiting membrane of some sections. The positive rate of VEGF was detected by X2 test during 4 weeks in diabetic group. The positive rate of VEGF expression in normal control group and diabetic group was analyzed statistically (P0.05). ConclusionRetina of diabetic rats showed obvious changes at 4 weeks: the thickness of retina became thinner, the space of vascular wall widened, and the expression of VEGF in the retina of early diabetic rats decreased at 4 weeks after the high expression of VEGF was found in the retina of early diabetic rats at 1 ~ 3 weeks. It is assumed that with the prolongation of the course of disease, the expression of Ang-1 will decrease with the increase of vascular permeability, while the expression of VEGF will be more and more as an osmotic factor, which plays an important role in vascular integrity. When the two are out of balance, blood vessel osmosis occurs, which leads to the release of factors that stimulate angiogenesis. This makes clear the expression of Ang-1 in the retina of early diabetes mellitus. It can be used as one of the early intervention guidelines for diabetic retinopathy.
【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R774.1

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