阿瓦斯汀抑制兔眼堿燒傷角膜新生血管的研究
發(fā)布時間：2018-10-19 11:46
【摘要】：目的： 通過研究阿瓦斯汀(Avastin)結膜下給藥對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,為臨床應用阿瓦斯汀治療角膜新生血管性疾病提供實驗依據(jù)。 方法： 選用成年新西蘭雄性大白兔60只(蘇州大學動物實驗中心),體重在2-3Kg之間,健康狀況良好,均取左眼作為實驗眼,隨機抽選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只兔左眼設為A正常對照組,成功造模的45只兔再隨機分為三組,每組15只,分別為B模型對照組(造模成功后不做治療),C新藥干預組(術后2小時結膜下注射2.5mg/0.1ml阿瓦斯汀),D常規(guī)治療照組(術后2小時結膜下注射地塞米松0.5mg/0.1ml),于堿燒傷后4、7、14天拍照記錄,觀察活體兔眼結膜充血、角膜水腫渾濁、上皮的完整性及新生血管的生長情況,定量計算角膜新生血管面積,并于三個時間點每組隨機取5只兔用空氣栓塞法處死,取實驗眼角膜行病理檢查及免疫組化檢測角膜VEGF和CD31的表達。 結果： 1、堿燒傷4天,造模組所有兔眼均出現(xiàn)明顯的炎癥反應,結膜充血水腫,角膜水腫渾濁,上皮不完整,B組角膜緣見少許新生血管長入,C、D組未發(fā)現(xiàn)有角膜新生血管,7天,造模組所有兔眼結膜充血明顯,角膜新生血管生長旺盛,自角膜緣呈毛刷樣向燒傷區(qū)爬行,10-14點區(qū)域新生血管出現(xiàn)最多。14天,角、結膜充血水腫減輕,角膜上皮修復,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,正常對照組角膜上皮完整,層次清晰,角膜基質(zhì)纖維排列整齊,無炎細胞及血管,術后4天造模組角膜上皮連續(xù)性中斷,上皮下及淺基質(zhì)層見少量新生血管芽,管腔少量血細胞,大量炎細胞主要聚集于角膜淺層,7天時角膜新生血管密集,并向深基質(zhì)層長入,管腔粗大且充滿血細胞。14天時,炎細胞減少,表面新生血管部分消退,基質(zhì)層見管徑粗大的血管,血細胞充盈,在不同時間點,C、D組之間差別無統(tǒng)計學差異,C、D組與B組之間比較有統(tǒng)計學差異。 3、角膜VEGF檢測結果：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)強陽性,14天時密度降低,三個時間點統(tǒng)計,C、D組之間、/EGF表達強度無統(tǒng)計學差異,C、D組VEGF表達強度較B組輕,與B組之間比較有統(tǒng)計學差異。 4、角膜CD31檢測結果示：CD31在正常兔眼角膜組織中無表達,造模組兔角膜中均有表達,7天時表達強陽性,各時間點C、D治療組陽性細胞數(shù)明顯低于模型對照組,差異有統(tǒng)計學意義。 結論： 1、兔眼角膜堿燒傷4天角膜開始有新生血管長入,燒傷后7天時結膜炎癥反應比較重,角膜水腫渾濁,新生血管生長旺盛,14天結膜炎癥反應減輕,角膜新生血管有所消退。 2、阿瓦斯汀與地塞米松對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組在三個不同時間點檢測到的新生血管、VEGF及CD31均顯著降低,C組與D組在三個不同的時間點檢測的各項指標無顯著差異。 3、阿瓦斯汀治療兔眼角膜新生血管簡單、安全、效果顯著,在觀察期內(nèi)未見并發(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.
【學位授予單位】：蘇州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R965
本文編號：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.
【學位授予單位】：蘇州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R965
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