阿瓦斯汀抑制兔眼堿燒傷角膜新生血管的研究
發(fā)布時(shí)間：2018-10-19 11:46
【摘要】：目的： 通過(guò)研究阿瓦斯汀(Avastin)結(jié)膜下給藥對(duì)兔眼堿燒傷角膜新生血管的影響,探索阿瓦斯汀治療角膜新生血管的安全性及其有效性,為臨床應(yīng)用阿瓦斯汀治療角膜新生血管性疾病提供實(shí)驗(yàn)依據(jù)。 方法： 選用成年新西蘭雄性大白兔60只(蘇州大學(xué)動(dòng)物實(shí)驗(yàn)中心),體重在2-3Kg之間,健康狀況良好,均取左眼作為實(shí)驗(yàn)眼,隨機(jī)抽選45只兔左眼用1mol/LNaOH溶液燒傷,建立堿燒傷角膜新生血管模型。未造模的15只兔左眼設(shè)為A正常對(duì)照組,成功造模的45只兔再隨機(jī)分為三組,每組15只,分別為B模型對(duì)照組(造模成功后不做治療),C新藥干預(yù)組(術(shù)后2小時(shí)結(jié)膜下注射2.5mg/0.1ml阿瓦斯汀),D常規(guī)治療照組(術(shù)后2小時(shí)結(jié)膜下注射地塞米松0.5mg/0.1ml),于堿燒傷后4、7、14天拍照記錄,觀察活體兔眼結(jié)膜充血、角膜水腫渾濁、上皮的完整性及新生血管的生長(zhǎng)情況,定量計(jì)算角膜新生血管面積,并于三個(gè)時(shí)間點(diǎn)每組隨機(jī)取5只兔用空氣栓塞法處死,取實(shí)驗(yàn)眼角膜行病理檢查及免疫組化檢測(cè)角膜VEGF和CD31的表達(dá)。 結(jié)果： 1、堿燒傷4天,造模組所有兔眼均出現(xiàn)明顯的炎癥反應(yīng),結(jié)膜充血水腫,角膜水腫渾濁,上皮不完整,B組角膜緣見(jiàn)少許新生血管長(zhǎng)入,C、D組未發(fā)現(xiàn)有角膜新生血管,7天,造模組所有兔眼結(jié)膜充血明顯,角膜新生血管生長(zhǎng)旺盛,自角膜緣呈毛刷樣向燒傷區(qū)爬行,10-14點(diǎn)區(qū)域新生血管出現(xiàn)最多。14天,角、結(jié)膜充血水腫減輕,角膜上皮修復(fù),角膜渾濁,中央燒傷區(qū)最為致密,角膜新生血管有所消退。 2、病理顯示,正常對(duì)照組角膜上皮完整,層次清晰,角膜基質(zhì)纖維排列整齊,無(wú)炎細(xì)胞及血管,術(shù)后4天造模組角膜上皮連續(xù)性中斷,上皮下及淺基質(zhì)層見(jiàn)少量新生血管芽,管腔少量血細(xì)胞,大量炎細(xì)胞主要聚集于角膜淺層,7天時(shí)角膜新生血管密集,并向深基質(zhì)層長(zhǎng)入,管腔粗大且充滿血細(xì)胞。14天時(shí),炎細(xì)胞減少,表面新生血管部分消退,基質(zhì)層見(jiàn)管徑粗大的血管,血細(xì)胞充盈,在不同時(shí)間點(diǎn),C、D組之間差別無(wú)統(tǒng)計(jì)學(xué)差異,C、D組與B組之間比較有統(tǒng)計(jì)學(xué)差異。 3、角膜VEGF檢測(cè)結(jié)果：堿燒傷4天,造模組所有兔眼角膜均出現(xiàn)VEGF,7天VEGF表現(xiàn)強(qiáng)陽(yáng)性,14天時(shí)密度降低,三個(gè)時(shí)間點(diǎn)統(tǒng)計(jì),C、D組之間、/EGF表達(dá)強(qiáng)度無(wú)統(tǒng)計(jì)學(xué)差異,C、D組VEGF表達(dá)強(qiáng)度較B組輕,與B組之間比較有統(tǒng)計(jì)學(xué)差異。 4、角膜CD31檢測(cè)結(jié)果示：CD31在正常兔眼角膜組織中無(wú)表達(dá),造模組兔角膜中均有表達(dá),7天時(shí)表達(dá)強(qiáng)陽(yáng)性,各時(shí)間點(diǎn)C、D治療組陽(yáng)性細(xì)胞數(shù)明顯低于模型對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義。 結(jié)論： 1、兔眼角膜堿燒傷4天角膜開(kāi)始有新生血管長(zhǎng)入,燒傷后7天時(shí)結(jié)膜炎癥反應(yīng)比較重,角膜水腫渾濁,新生血管生長(zhǎng)旺盛,14天結(jié)膜炎癥反應(yīng)減輕,角膜新生血管有所消退。 2、阿瓦斯汀與地塞米松對(duì)兔眼堿燒傷后形成的新生血管都有很好的抑制作用,與B造模組相比,C、D組在三個(gè)不同時(shí)間點(diǎn)檢測(cè)到的新生血管、VEGF及CD31均顯著降低,C組與D組在三個(gè)不同的時(shí)間點(diǎn)檢測(cè)的各項(xiàng)指標(biāo)無(wú)顯著差異。 3、阿瓦斯汀治療兔眼角膜新生血管簡(jiǎn)單、安全、效果顯著,在觀察期內(nèi)未見(jiàn)并發(fā)癥發(fā)生。
[Abstract]:Purpose: Objective To explore the safety and efficacy of Avastin in the treatment of corneal neovascularization by studying the effect of Avastin on corneal neovascularization in rabbits, and to provide an experiment for the clinical application of Avastin in the treatment of corneal neovascularization. Basis. Methods: 60 adult New Zealand white rabbits were selected (Suzhou University Animal Experiment Center), the body weight was 2-3Kg, the health condition was good, the left eye was taken as the experimental eye, 45 rabbits were randomly selected to burn the left eye with 1mol/ L NaOH solution, and alkali burn was established. The corneal neovascularization model was established. 15 rabbits were randomly divided into three groups, 15 rabbits in each group were randomly divided into three groups, 15 rabbits in each group were respectively B model control group (not treated after the model was successful), and the C drug intervention group (2 hours after operation) was injected with 2. 5mg/ 0. 1 ml of Avastin, D conventional treatment group (dexamethasone 0.5 mg/ 0. 1ml at 2 hours after operation), 4, 7 and 14 days after alkali burn, observation of conjunctival congestion, corneal edema, integrity of epithelium and growth of newborn blood vessels were observed, and quantitative calculation was carried out. The corneal neovascularization area was randomly taken at three time points, 5 rabbits were killed by air embolism method, the pathological examination and immunohistochemistry were used to detect corneal VEGF. 鍜孋D Results: 1. After 4 days of alkali burn, there were obvious inflammatory response, conjunctival congestion edema, corneal edema and incomplete epithelium in all rabbit eyes. A few new blood vessels were seen in group B limbal, C, D. The corneal neovascularization was not found in the group, 7 days, the conjunctival congestion of all rabbits in the building module was obvious, the corneal neovascularization was vigorous, the brush-like vein appeared on the limbal edge to crawl into the burn area, and the newly-formed blood vessel in the area of 10-14 points appeared the most. 14 days, the angle, conjunctival hyperemia and edema were alleviated, and the corneal epithelium was repaired. Corneal opacity, central burn area most In the normal control group, the corneal epithelium is intact, the level is clear, the corneal stroma fibers are arranged in order, there is no inflammatory cells and blood vessels, the continuity of corneal epithelium is interrupted, the upper subcutaneous layer and the shallow matrix are formed on the 4-day post-operation. The layer is seen in a small amount of fresh blood vessel bud, small amount of blood cells in the tube cavity, a large number of inflammatory cells are mainly concentrated on the superficial layer of the cornea, the corneal neovascularization is dense at 7 days, and the deep matrix layer is long inserted, the tube cavity is large and full of blood cells. 14 days, the inflammatory cells are reduced, the surface fresh blood vessel part is resolved, There was no statistical difference between C and D groups at different time points. There was a statistically significant difference between group C, group D and group B. 3. The results of corneal VEGF detection: 4 days after alkali burn, VEGF was observed in all eyes of all rabbits, 7 days VEGF expression was strongly positive, the density was decreased at 14 days, and there was no statistical difference between the three time points statistics, C and D groups and/ EGF expression intensity. The expression of VEGF in group C and D The results showed that CD31 was not expressed in the cornea of normal rabbit eyes, and in the cornea of the module rabbits, the expression was strongly positive at 7 days, and the C and D treatment groups at each time point were positive. positive fine The number of cells was significantly lower than that in the model control group, and the difference was statistically significant. Conclusion: 1. The cornea of the cornea in the cornea of rabbit cornea began to grow in 4 days, the conjunctivitis was heavier in 7 days after burn, and the corneal edema was cloudy and new. In addition, Avastin and dexamethasone have a good inhibitory effect on new blood vessels formed after ocular alkali burn in rabbits, and C, D compared with B-building modules. Neovascular, VEGF and CD31 detected at three different time points There was no significant difference between group C and group D at three different time points.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R965
本文編號(hào)：2281020
[Abstract]:Purpose: Objective To explore the safety and efficacy of Avastin in the treatment of corneal neovascularization by studying the effect of Avastin on corneal neovascularization in rabbits, and to provide an experiment for the clinical application of Avastin in the treatment of corneal neovascularization. Basis. Methods: 60 adult New Zealand white rabbits were selected (Suzhou University Animal Experiment Center), the body weight was 2-3Kg, the health condition was good, the left eye was taken as the experimental eye, 45 rabbits were randomly selected to burn the left eye with 1mol/ L NaOH solution, and alkali burn was established. The corneal neovascularization model was established. 15 rabbits were randomly divided into three groups, 15 rabbits in each group were randomly divided into three groups, 15 rabbits in each group were respectively B model control group (not treated after the model was successful), and the C drug intervention group (2 hours after operation) was injected with 2. 5mg/ 0. 1 ml of Avastin, D conventional treatment group (dexamethasone 0.5 mg/ 0. 1ml at 2 hours after operation), 4, 7 and 14 days after alkali burn, observation of conjunctival congestion, corneal edema, integrity of epithelium and growth of newborn blood vessels were observed, and quantitative calculation was carried out. The corneal neovascularization area was randomly taken at three time points, 5 rabbits were killed by air embolism method, the pathological examination and immunohistochemistry were used to detect corneal VEGF. 鍜孋D Results: 1. After 4 days of alkali burn, there were obvious inflammatory response, conjunctival congestion edema, corneal edema and incomplete epithelium in all rabbit eyes. A few new blood vessels were seen in group B limbal, C, D. The corneal neovascularization was not found in the group, 7 days, the conjunctival congestion of all rabbits in the building module was obvious, the corneal neovascularization was vigorous, the brush-like vein appeared on the limbal edge to crawl into the burn area, and the newly-formed blood vessel in the area of 10-14 points appeared the most. 14 days, the angle, conjunctival hyperemia and edema were alleviated, and the corneal epithelium was repaired. Corneal opacity, central burn area most In the normal control group, the corneal epithelium is intact, the level is clear, the corneal stroma fibers are arranged in order, there is no inflammatory cells and blood vessels, the continuity of corneal epithelium is interrupted, the upper subcutaneous layer and the shallow matrix are formed on the 4-day post-operation. The layer is seen in a small amount of fresh blood vessel bud, small amount of blood cells in the tube cavity, a large number of inflammatory cells are mainly concentrated on the superficial layer of the cornea, the corneal neovascularization is dense at 7 days, and the deep matrix layer is long inserted, the tube cavity is large and full of blood cells. 14 days, the inflammatory cells are reduced, the surface fresh blood vessel part is resolved, There was no statistical difference between C and D groups at different time points. There was a statistically significant difference between group C, group D and group B. 3. The results of corneal VEGF detection: 4 days after alkali burn, VEGF was observed in all eyes of all rabbits, 7 days VEGF expression was strongly positive, the density was decreased at 14 days, and there was no statistical difference between the three time points statistics, C and D groups and/ EGF expression intensity. The expression of VEGF in group C and D The results showed that CD31 was not expressed in the cornea of normal rabbit eyes, and in the cornea of the module rabbits, the expression was strongly positive at 7 days, and the C and D treatment groups at each time point were positive. positive fine The number of cells was significantly lower than that in the model control group, and the difference was statistically significant. Conclusion: 1. The cornea of the cornea in the cornea of rabbit cornea began to grow in 4 days, the conjunctivitis was heavier in 7 days after burn, and the corneal edema was cloudy and new. In addition, Avastin and dexamethasone have a good inhibitory effect on new blood vessels formed after ocular alkali burn in rabbits, and C, D compared with B-building modules. Neovascular, VEGF and CD31 detected at three different time points There was no significant difference between group C and group D at three different time points.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R965
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