阿瓦斯汀不同的给药途径对兔角膜新生血管及角膜超微结构的影响

发布时间：2018-04-27 18:50

本文选题：角膜 + 新生血管　；参考：《南昌大学》2011年硕士论文

【摘要】：目的：通过研究阿瓦斯汀不同的给药途径分别对兔角膜新生血管及超微结构的影响,探索阿瓦斯汀治疗角膜新生血管较安全持久有效的给药途径,为临床应用阿瓦斯汀治疗角膜新生血管性疾病提供实验依据。方法：选用健康新西兰大白兔55只,兔龄2.5-3个月,雌雄不限。随机选50只兔左眼用1mol/L氢氧化钠溶液烧伤,建立碱烧伤角膜新生血管动物模型,造模成功后选取48只随机分为A点眼液组12只(5mg/ml,3次/日)、B结膜下注射组12只(25mg/ml,1次/周),C角膜基质注射组12只(25mg/ml,1次/周),D模型对照组12只(不用药),选取未造模2只兔为空白对照,于碱烧伤术后1天、4天、给药后一周、二周、四周观察造模兔眼结膜充血、角膜浑浊、新生血管生长情况及角膜组织的完整性,并进行眼前节照相,并测量各试验兔眼角膜新生血管的长度及分布钟点位数以计算角膜新生血管面积,与给药后一周、二周、四周三个时间点后用空气栓塞法每组各处死4只试验用兔,处死后即刻抽取试验眼房水约0.1m1用于检测房水中的VEGF蛋白的含量,并取新生血管生长最旺盛的角膜组织分别固定,待做电镜、免疫组化(角膜组织中CD31)等检测。结果： 1、在碱烧伤后各观察时间点房水中VEGF的浓度均高于正常兔眼水平,碱烧伤后11天内房水中VEGF蛋白含量增加迅速,约18天左右时房水中VEGF蛋白含量达到最高水平,之后有所下降,到32天时达到一个较稳定的水平,不同处理方法之间相比较在三个时间点差别均有统计学意义。 2、碱烧伤角膜新生血管在碱烧伤后12天内生长迅速,14天时有所消退,之后新生血管趋于相对稳定状态,不同处理方法之间相比较在三个时间点差别均有统计学意义。 3、免疫组化染色结果示：CD31在正常兔眼角膜组织中未有表达,各治疗组阳性细胞数明显少于模型对照组,差异有统计学意义。 4、电镜检查结果：ABD组角膜超微结构在一周、二周、四周时除碱烧伤损伤外无明显其它改变,在给药后第二周、四周时C组角膜超微结构损伤要重于ABD组。结论： 1、兔眼房水中VEGF蛋白含量在碱烧伤后11天内增长较快,至18天左右时达到高峰水平,之后VEGF有所下降,最后趋于较稳定水平。 2、点眼液(5mg/ml,3次/日),结膜下注射(25mg/ml,1次/周),角膜基质注射(25mg/ml,1次/周)三种给药途径都对碱烧伤角膜新生血管增殖期动物模型有较好的抑制作用,同时也能减轻角膜的混浊。 3、点眼液与结膜下注射给药途径简单安全、效果相对稳定,在观察期内未见对角膜超微结构的产生明显影响。 4、角膜基质注射给药途径虽短期效果显著,但在观察期内对角膜超微结构产生较明显的影响。
[Abstract]:Objective: By studying the effects of different administration routes of Awa statin on corneal neovascularization and ultrastructure in rabbits, we explored the safe and effective way of administration of Awa statin in the treatment of corneal neovascularization. To provide experimental evidence for clinical treatment of corneal neovascular diseases with Awa statin. Methods: A total of 55 healthy New Zealand white rabbits (2.5-3 months old) were selected. A corneal neovascularization model was established in 50 rabbits with 1mol/L sodium hydroxide solution burn. 48 rats were randomly divided into A point group (n = 12) with 5 mg / ml / d subconjunctival injection group (n = 12) with 25 mg / ml once a week / week injection group (n = 12) and control group (n = 12). Rabbits were used as blank control. The conjunctival congestion, corneal opacification, neovascularization and corneal tissue integrity were observed one week, two weeks after alkali burn and one week, two weeks after administration. The corneal neovascularization area was calculated by measuring the length of corneal neovascularization and the number of hours of corneal neovascularization in each group. Four experimental rabbits were killed in each group by air embolization one week, two weeks and four weeks after administration of the drug. About 0.1m1 was extracted immediately after death to detect the content of VEGF protein in aqueous humor, and the corneal tissues with the most vigorous neovascularization were fixed respectively, and were examined by electron microscope and immunohistochemistry (CD31 in corneal tissue). Results: 1. The concentration of VEGF in aqueous humor was higher than that in normal rabbit eyes at all time points after alkali burn. The content of VEGF protein in aqueous humor increased rapidly within 11 days after alkali burn, and the content of VEGF protein in aqueous humor reached the highest level at about 18 days, and then decreased. At 32 days, a relatively stable level was reached, and the differences among different treatment methods were statistically significant at three time points. 2. Corneal neovascularization after alkali burn subsided rapidly within 12 days after alkali burn, then the neovascularization tended to be relatively stable. There were significant differences among different treatment methods at three time points. 3. The results of immunohistochemical staining showed that there was no expression of CD31 in normal rabbit cornea, and the number of positive cells in each treatment group was significantly lower than that in model control group (P < 0.05). (4) the ultrastructure of cornea in group C was more serious than that in group ABD at the second week after administration of the drug, and there was no obvious change of corneal ultrastructure except alkali burn injury at one week, two weeks and four weeks after administration of the drug. Conclusion: 1. The content of VEGF protein in aqueous humor of rabbit eyes increased rapidly within 11 days after alkali burn, reached the peak level at about 18 days, then VEGF decreased and finally became stable. 2, 5 mg / ml / day, 5 mg / ml / day, 25 mg / ml / week, and 25 mg / ml / week respectively) all of the three ways have a good inhibitory effect on corneal neovascularization model of alkali burn, and can also reduce corneal opacity. 3. The route of injection of point eye liquid and subconjunctival injection was simple and safe, the effect was relatively stable, and there was no obvious effect on the ultrastructure of cornea during the observation period. 4. The short-term effect of corneal stroma injection was remarkable, but it had obvious effect on corneal ultrastructure during the observation period.
【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R772.2

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