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不同药物对硅油乳化影响的体外研究

In Vitro Study on the Effects of Different Medicine to Silicone Oil Emulsification

【作者】 陈晓君

【导师】 王文战;

【作者基本信息】 郑州大学 , 眼科学, 2011, 硕士

【摘要】 眼科用硅油的材料为聚二甲基硅氧烷(Polydimethylsiloxane, PDMS).在常温下,其屈光指数为1.404,与玻璃体屈光指数相近,与晶状体的屈光率基本相同。硅油具有光学透明性好、物理性能稳定、生理惰性、生物相容性好、作用时间持久等优点,作为玻璃体替代物现已广泛应用于临床,用于各种复杂的眼外伤手术及玻璃体视网膜手术中。但是硅油长时间的眼内填充会引起许多并发症,如角膜变性、并发性白内障、继发性青光眼、硅油乳化等,其中硅油乳化的发生率约为0.7%-40%。硅油乳化的发生受许多因素的影响,其发生的原因目前尚无明确的定论,成为国内外众多学者研究的热门课题。本实验通过体外研究分析不同药物:葡萄糖、玻璃酸酶、透明质酸钠、维生素B12及维拉帕米对硅油乳化的影响,为今后硅油乳化防治的深入研究及眼内填充物的性状改善提供依据,以指导临床用药尤其是眼内用药。第一部分不同药物对硅油乳化的影响材料与方法使用特制5ml容量瓶建立体外眼模型,于其中加入硅油(法国ARCAD公司Arciolane 5500cs) 4.0ml和不同药物:平衡盐溶液(balanced salt solution, BSS)0.5ml作为对照组,葡萄糖、玻璃酸酶、透明质酸钠、维生素B12、维拉帕米的BSS溶液各0.5ml作为实验组,在37℃恒温气浴摇床中振荡,速度120转/分。分别于1w,2w,4w,8w观察各组硅油乳化情况并计数乳化硅油颗粒数目。结果1.不同药物不同时间硅油乳化颗粒数目比较,差异均有统计学意义(P<0.05),表示药物不同,硅油乳化颗粒数目不同;随着时间的延长,硅油乳化颗粒数目逐渐增加。2.高渗葡萄糖组与BSS组各个时间硅油乳化颗粒数目比较,差异均无统计学意义(P>0.05),高渗葡萄糖组硅油乳化颗粒数目与BSS组无明显差别。3.玻璃酸酶组与BSS组1W、2W、4w时比较,差异均无统计学意义(P>0.05),硅油乳化颗粒数目与BSS组无差别;8w时差异有统计学意义(P<0.05),玻璃酸酶组硅油乳化颗粒数目多于BSS组。4.透明质酸钠组与BSS组1W、2W、4w时比较,差异均有统计学意义(P<0.05),硅油乳化颗粒数目少于BSS组;8w时差异有统计学意义(P<0.05),硅油乳化颗粒数目多于BSS组。5.维生素B12组与BSS组1w时比较,差异无统计学意义(P>0.05),硅油乳化颗粒数目与BSS组无明显差别;2W、4W、8w时比较,差异均有统计学意义(P<0.05),硅油乳化颗粒数目多于BSS组。6.维拉帕米组与BSS组各个时间硅油乳化颗粒数目比较,差异均有统计学意义(P<0.05),硅油乳化颗粒数目明显多于BSS组。结论1.体外研究虽然不能模拟活体的代谢,但是可以统一众多繁杂因素,有利于实验研究,分析单纯药物作用下对硅油乳化的影响。2.随着时间的延长,硅油乳化颗粒数目逐渐增加。高渗葡萄糖溶液对硅油乳化无明显影响;玻璃酸酶随着作用时间的延长,可以增加硅油乳化;透明质酸钠可以影响远期硅油乳化量;维生素B12注射液和维拉帕米注射液可以促进硅油乳化。第二部分不同药物对乳化硅油的影响材料与方法使用特制5ml容量瓶建立体外眼模型,于其中加入硅油(法国ARCAD公司Arciolane 5500cs)4.0ml口BSS液0.3ml重复配置5管,置于37℃恒温气浴摇床中振荡,速度120转/分。2周后显微镜下观察出现乳化硅油颗粒,且数目相近。在乳化的硅油中分别加入不同药物(具体同第一部分),配足0.5ml的液体和乳化硅油4.0ml。在37℃恒温气浴摇床中振荡,速度120转/分。分别于1w,2w,4w,8w观察各组硅油乳化情况并计数乳化硅油颗粒数目。结果1.不同药物不同时间硅油乳化颗粒数目比较,差异均有统计学意义(P<0.05),表示药物不同,硅油乳化颗粒数目不同;随着时间的延长,硅油乳化颗粒数目逐渐增加。2.高渗葡萄糖组、玻璃酸酶组、透明质酸钠组分别与BSS组不同时间两两比较,差异均无统计学意义(P>0.05),各组硅油乳化颗粒数目与BSS组无明显差别;维生素B12组与BSS组不同时间两两比较,在8w时,差异有统计学意义(P<0.05),硅油乳化颗粒数目多于BSS组;维拉帕米组与BSS组不同时间两两比较,4W、8w时,差异有统计学意义(P<0.05),硅油乳化颗粒数目多于BSS组。结论随着时间的延长,硅油乳化颗粒数目逐渐增加。高渗葡萄糖溶液、玻璃酸酶、透明质酸钠对已乳化硅油的进一步乳化无明显影响。维生素B12注射液和维拉帕米注射液具有促进乳化硅油进一步乳化的作用。

【Abstract】 The silicone oil material used in eye is Polydimethylsiloxane (PDMS). The refractive index is 1.404 at the room temperature, which is similar to vitreous body and lens. Silicone oil has good optical transparency, stable physical properties, physical inertia, good biocompatibility and long-lasting effects. As a substitute for the vitreous body, silicone oil has been widely used in clinic for the surgery of complex ocular trauma and vitreoretinal diseases. However, the eye filled with silicone oil for a long time can cause many complications, such as corneal degeneration, complicated cataract, secondary glaucoma, silicone oil emulsification, and so on. The incidence of silicone oil emulsification is about 0.7% to 40%. The occurrence of silicone oil emulsion is affected by many factors. Nowadays there is no clear conclusion for the mechanism. It becomes a hot topic to study for many scholars at home and abroad.The experimental study was to analyze the effects of different medicine on silicone oil emulsification in vitro, including glucose, hyaluronidase, hyaluronic acid, vitamin B12 and verapamil. This study provided the basis of the prevention and treatment of silicone oil emulsification, which improved the characteristics of intraocular tamponde material for the future. It also guided clinical medication, especially eye treatment. Part I:The effects of different medicine on silicone oil emulsificationMaterials and MethodsThe establishment of in vitro model of the human eye with 5ml volumetric flask, which was to include silicone oil 4.0ml and different medicine:balanced salt solution (BSS) 0.5ml as a control group,0.5ml mixture of BSS with glucose, hyaluronidase, hyaluronic acid, vitamin B12 and verapamil as experimental groups. The chambers were then placed on a horizontal rotating shaker at a rate of 120 r min and incubated at 37℃. Silicone oil emulsification conditions were observed and quantified by dark field microscopy, digital photography at 1 week,2 week,4 week and 8 week.Results1.The number of silicone oil emulsion particles was significantly different between different groups at different time (P<0.05). The results showed that differential number of silicone oil emulsion particles resulted from different medicine and the emulsion particles were increased with time.2. The number of silicone oil emulsion particles was no difference between hypertonic glucose group and BSS group at each time point. The results did not show statistically significant (P>0.05).3. The number of silicone oil emulsion particles was no difference between hyaluronidase group and BSS group at 1 week,2 week and 4 week (P>0.05). While the difference was statistically significant at 8 week (P<0.05), and the hyaluronidase group had more silicone oil emulsion particles than BSS group.4. Compared with BSS group, the number of silicone oil emulsion particles of hyaluronic acid group was less than BSS group at 1 week,2 week and 4 week. The results showed statistically significant (P<0.05). The difference was statistically significant at 8 week (P<0.05), while the group of hyaluronic acid had more silicone oil emulsion particles than BSS.5. Compared with BSS group, the number of silicone oil emulsion particles was no difference between vitamin B12 group and BSS group at 1 week. The result did not show statistically significant(P> 0.05). The difference was statistically significant at 2 week,4 week and 8 week (P<0.05). The group of vitamin B12 had more silicone oil emulsion particles than BSS at these three time point.6. The number of silicone oil emulsion particles of verapamil group was more than that of BSS group at each time. The results showed statistically significant (P< 0.05).Conclusions1. Although in vitro study can not simulate the in vivo environment, it can be unified many complicated factors. The method is conducive to experimental study and can be used to analyze the effects on the silicone oil emulsion under the action of simple medicine.2. The emulsion particles are increased with time. Hypertonic glucose solution has no significant effect on the silicone oil emulsion. The role of hyaluronidase can increase the silicone oil emulsion with time. Hyaluronic acid can affect the amount of long-term silicone oil emulsion. Vitamin B12 injection and verapamil injection can promote emulsification of silicone oil.PartⅡ:The effects of different medicine on emulsified silicone oil Materials and MethodsThe establishment of in vitro model of the human eye with 5ml volumetric flask, which was to added silicone oil 4.0ml and BSS 0.3ml. Each group was repeated configuration 5 pipes. The chambers were then placed on a horizontal rotating shaker at a rate of 120 r/min and incubated at 37℃. Silicone oil emulsion particles appeared similar number by dark field microscopy after two weeks. Then different medicine which was same of the first part was joined into emulsified silicone oil, and at last every chamber had mixture 0.5ml and emulsified silicone oil 4.0 ml. The chambers were then placed on a horizontal rotating shaker at a rate of 120 r/min and incubated at 37℃. Silicone oil emulsification conditions were observed and quantified by dark field microscopy, digital photography at 1 week,2 week,4 week and 8 week.Results1.The number of silicone oil emulsion particles was significantly different with different groups at different time (P<0.05). The results showed that differential number of silicone oil emulsion particles resulted from different medicine and the emulsion particles were increased with time.2. Hypertonic glucose group, hyaluronidase group, hyaluronic acid group had no difference with BSS group at each time. The results did not show statistically significant (P>0.05). Compared with BSS group, the number of silicone oil emulsion particles of vitamin B12 group was more than that of BSS group at 8 week. The result showed statistically significant (P<0.05). Compared with BSS group, the number of silicone oil emulsion particles of verapamil group was more than that of BSS group at 4 week and 8 week. The results showed statistically significant (P< 0.05).ConclusionsThe emulsion particles of emulsified silicone oil are increased with time. There is no significant effect on further emulsion of emulsified silicone oil with hypertonic glucose solution, hyaluronidase and hyaluronic acid. Vitamin B12 injection and verapamil injection can promote further emulsion of emulsified silicone oil.

  • 【网络出版投稿人】 郑州大学
  • 【网络出版年期】2012年 04期
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