發(fā)布時間：2018-05-20 23:46

  本文選題：過氧化物酶體增生物激活受體-γ + 糖尿病性視網(wǎng)膜病變��； 參考：《瀘州醫(yī)學(xué)院》2010年碩士論文

【摘要】：目的：建立糖尿病大鼠動物模型,給予過氧化物酶體增生物激活受體-γ(peroxisome proliferator-activated receptor-gamma, PPAR-y)激動劑羅格列酮對大鼠進行干預(yù),觀察其血清和視網(wǎng)膜中單核細胞趨化蛋白-1(monocyte chemotactic protein-1, MCP-1)表達及視網(wǎng)膜微血管的變化,探討外源性PPAR-γ激動劑對早期糖尿病性視網(wǎng)膜病變的保護作用及其機制。方法：腹腔注射鏈脲佐菌素(streptozotocin, STZ)制備糖尿病(diabetes mellitus, DM)動物模型。選用健康雄性Wistar大鼠90只,隨機分為三組：正常對照組(C組,n=30),糖尿病模型空白對照組(D組,n=30),糖尿病模型羅格列酮干預(yù)組(R組,n=30)；糖尿病模型羅格列酮干預(yù)組每日給予羅格列酮3mg/kg灌胃,正常對照組和糖尿病模型空白對照組則給予同等劑量的生理鹽水灌胃(相同容積)。所有大鼠每周測體重和空腹血糖兩次。分別于給藥后4w、8w和12w處死各組大鼠,采集大鼠血液及眼球標(biāo)本；行視網(wǎng)膜消化鋪片,觀察視網(wǎng)膜微血管形態(tài),并行內(nèi)皮細胞(endothelial cell, E)和周細胞(perithelial cell, P)計數(shù)、計算E/P值；伊文思藍法測定血-視網(wǎng)膜屏障的通透性；免疫組化法檢測視網(wǎng)膜中MCP-1的陽性表達；酶聯(lián)免疫吸附法(enzyme linked immunosorbent assay, ELISA)定量測定血清中MCP-1的含量。結(jié)果：1.各時間點D組和R組大鼠體重均明顯低于C組；空腹血糖均明顯高于C組(P＜0.01)。2.與相應(yīng)的C組比較：D組4w開始出現(xiàn)體重減輕,血-視網(wǎng)膜屏障通透性增加,血清及視網(wǎng)膜中MCP-1的表達增多；8w開始出現(xiàn)視網(wǎng)膜毛細血管壁周細胞減少,內(nèi)皮細胞增多,差異均具有統(tǒng)計學(xué)意義(P0.01)；且隨著時間的延長,視網(wǎng)膜微血管病變程度逐漸加重,呈時間依賴性改變。3.應(yīng)用羅格列酮干預(yù)后,視網(wǎng)膜微血管病理損害明顯減輕。與相應(yīng)的D組比較：R組4w開始出現(xiàn)體重增加,血.視網(wǎng)膜屏障通透性降低,血清及視網(wǎng)膜中MCP.1的表達減少,8w開始出現(xiàn)視網(wǎng)膜毛細血管壁周細胞增多,內(nèi)皮細胞減少,差異均具有統(tǒng)計學(xué)意義(P＜0.01)；且隨著干預(yù)時間的延長,視網(wǎng)膜微血管病變程度逐漸減輕,呈時間依賴性改變。結(jié)論：1.正常大鼠血清及視網(wǎng)膜中存在少量的MCP.1表達。2.羅格列酮可能通過激活PPAR-γ、下調(diào)炎性因子MCP.1的表達對早期糖尿病性視網(wǎng)膜病變起到一定的保護作用,可能成為其早期防治的新靶點。3.應(yīng)用STZ腹腔注射可成功復(fù)制糖尿病動物模型,簡便快捷；模型病變典型,成功率高,死亡率低。
[Abstract]:Aim: to establish an animal model of diabetic rats and to treat rats with rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-Y) agonist. To observe the expression of monocyte chemoattractant protein-1 chemotactic protein-1 (MCP-1) and the changes of retinal microvessels in serum and retina, and to explore the protective effect of exogenous PPAR- 緯 agonist on early diabetic retinopathy and its mechanism. Methods: streptozotocin (STZZ) was injected intraperitoneally to establish diabetic Mellitus (DM) animal model. 90 healthy male Wistar rats were selected. The rats were randomly divided into three groups: normal control group (n = 30), control group C (n = 30), control group D (n = 30), rosiglitazone group (n = 30) and rosiglitazone group (n = 30), and rosiglitazone group (n = 30) were given rosiglitazone 3mg/kg daily. Normal control group and diabetes model blank control group were given the same dose of normal saline (same volume). All rats were measured twice a week for body weight and fasting blood glucose. Rats in each group were killed at 4 weeks and 12 weeks after administration, blood and eyeball samples were collected, retinal microvessel morphology was observed, endothelium cell endothelial cell (E) and pericyte periepithelial cell (P) count, and E / P value were calculated. The permeability of blood-retinal barrier was determined by Evans blue method, the positive expression of MCP-1 in retina was detected by immunohistochemical method, and the content of MCP-1 in serum was determined quantitatively by enzyme linked immunosorbent assay, ELISA) by enzyme linked immunosorbent assay (Elisa). The result is 1: 1. At each time point, the body weight of group D and group R were significantly lower than those of group C, and the fasting blood glucose was significantly higher than that of group C (P < 0.01). Compared with the corresponding group C, the weight loss and the permeability of blood-retinal barrier began to appear in group C at 4 weeks, and the expression of MCP-1 in serum and retina began to decrease and endothelial cells increased at 8 weeks. The difference was statistically significant (P 0.01), and with the extension of time, the degree of retinal microangiopathy gradually increased, showing a time dependent change of .3. After treated with rosiglitazone, the pathological damage of retinal microvessels was significantly alleviated. Compared with the corresponding group D, the weight gain and blood began to appear in the group of 4 weeks. The retinal barrier permeability was decreased, and the expression of MCP.1 in serum and retina began to increase at 8 weeks, and the endothelial cells decreased, the difference was statistically significant (P < 0.01), and with the prolongation of the intervention time, the retinal capillary pericytes increased and the endothelial cells decreased (P < 0.01). The degree of retinal microangiopathy gradually decreased, showing a time-dependent change. Conclusion 1. There is a small amount of MCP.1 expression. 2. 2 in normal rat serum and retina. Rosiglitazone may play a protective role in early diabetic retinopathy by activating PPAR- 緯 and down-regulating the expression of inflammatory factor MCP.1. Rosiglitazone may be a new target for early prevention and treatment of diabetic retinopathy. STZ intraperitoneal injection can be used to successfully reproduce diabetic animal model, which is simple and fast, typical pathological changes, high success rate and low mortality.
【學(xué)位授予單位】：瀘州醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2010
【分類號】：R774.1

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