热门搜索: 论文 发表 社科期刊 北大核心 南大核心 cssci 科技期刊 教育

当前位置:主页 > 医学论文 > 眼科论文 >

RGD多肽水凝胶的制备及其在抑制青光眼滤过术后瘢痕化中的作用

发布时间:2019-03-15 20:06  文章来源:笔耕文化传播
【摘要】: 目的研究RGD小分子多肽的合成,RGD多肽水凝胶的制备及其在兔眼结膜下和前房中的生物相容性。方法通过标准的9-芴甲氧羰基(FMOC)固相肽合成技术(SPPS)合成含有RGD序列(精氨酸-甘氨酸-天门冬氨酸)和N-9-芴甲氧羰基(FMOC)的小分子多肽。将这种超分子多肽溶于蒸馏水,多肽通过FMOC端基的π-π键堆叠作用自组装成具有三维结构的多肽水凝胶。再把这种RGD多肽水凝胶注射在兔眼结膜下和前房中,通过临床观察和组织学研究对这种新型多肽水凝胶进行生物相容性研究。结果成功合成了含有氨基酸RGD序列(精氨酸-甘氨酸-天门冬氨酸)的小分子多肽,多肽能通过自组装行为得到可注射的RGD多肽水凝胶。RGD多肽水凝胶在兔眼结膜下和前房中具有良好的生物相容性。结论RGD多肽水凝胶在兔眼结膜和前房中生物相容性良好,并具有构建眼部植入性的药物缓释系统的应用潜力,这种新型生物材料及其控释系统将在眼前节疾病比如青光眼,虹膜睫状体炎,角膜病的治疗中发挥作用。 目的一种新型的自组装多肽水凝胶应用于兔眼滤过术后结膜下,使其能达到降低术后眼内压(IOP),延长滤过泡生存时间,和促进滤过术后伤口正常愈合的目的。 方法合成RGD自组装的多肽水凝胶。进行两组动物实验:1)兔眼行滤过术后结膜下注射多肽水凝胶,不同时间段处死动物,应用实时定量逆转录聚合酶链式反应(RT-PCR)测其滤过区域的结缔组织生长因子(CTGF) mRNA的表达水平。2)兔眼行滤过术后结膜下注射多肽水凝胶,不同时间段对兔眼进行眼内压,裂隙灯显微镜,超声生物显微镜(UBM)的观察,并在21天后处死动物,对兔眼进行组织学分析。 结果结缔组织生长因子(CTGF) mRNA的表达水平和眼内压(IOP)在术后21天均明显比对照组低。手术区域滤过泡形态和超声生物显微镜(UBM)都提示滤过泡和滤过道功能良好。病理组织学分析提示RGD多肽水凝胶能够保持兔眼滤过术后滤过泡和滤过道的形态结构,减少瘢痕形成,并使手术伤口正常愈合。结论RGD多肽水凝胶能够在兔眼滤过术后降低结缔组织生长因子(CTGF) mRNA的表达水平,延长滤过泡生存时间,抑制滤过道的瘢痕形成,使眼内压持续维持较低水平。RGD多肽水凝胶为防止滤过术后滤过道瘢痕化提供了新的治疗途径。 目的构建5-FU RGD多肽水凝胶控释系统,研究该控释系统的体内外释药情况及抑制兔眼滤过术后瘢痕化的作用。方法合成含有RGD序列(精氨酸-甘氨酸-天门冬氨酸)和N-9-芴甲氧羰基(FMOC)的小分子多肽,多肽通过自组装行为得到RGD多肽水凝胶,并构建5-FU RGD多肽水凝胶控释系统。紫外分光光度计检测控释系统的体外释药情况。高效液相(HPLC)色谱仪检测5-FU RGD多肽水凝胶控释系统的兔眼内药代动力学情况。将5-FU RGD多肽水凝胶控释系统植入于行滤过术后的兔眼结膜下,不同时间段对兔眼进行眼内压,裂隙灯显微镜等临床观察,并于3至28天不同时间段处死动物,对兔眼进行组织学分析。结果5-FU能从RGD多肽水凝胶控释系统中缓慢释放,体内外释药平稳、高效,无突释现象。该控释系统能使兔眼眼内压(IOP)在术后28天均明显低于对照组,明显减少5-FU对周围正常眼组织的毒副作用,手术区域滤过泡形态提示滤过泡和滤过道的滤过功能良好。病理组织学分析提示RGD多肽水凝胶能够保持兔眼滤过术后滤过泡和滤过道的形态结构,明显减少α-肌动蛋白(α-SMA)的表达和胶原沉积。结论5-FU能够从RGD多肽水凝胶中缓慢释放,将5-FU RGD自组装多肽水凝胶应用于兔眼滤过术后,不仅能够避免频繁的结膜下注射5-FU,明显减少5-FU对周围正常眼组织的毒副作用,而且能够控制滤过术后眼内压及抑制滤过术后瘢痕化。5-FU RGD多肽水凝胶控释系统为防止滤过术后滤过道瘢痕化提供了新的治疗途径。
[Abstract]:Objective To study the synthesis of RGD small molecule polypeptide, the preparation of RGD polypeptide hydrogel and the biocompatibility of RGD polypeptide hydrogel in the subconjunctival and anterior chamber of rabbits. Methods Small-molecule polypeptides containing RGD (Arginine-Glycine-Aspartate) and N-9-methoxoxy-base (FMOC) were synthesized by standard 9-methoxyphenyl (FMOC) solid-phase peptide synthesis (SPPS). The super-molecular polypeptide is dissolved in distilled water, and the polypeptide is self-assembled into a polypeptide hydrogel with a three-dimensional structure by a carbon-carbon bond stacking function of the FMOC end group. The RGD polypeptide hydrogel was then injected into the subconjunctival and anterior chamber of the rabbit, and the biological compatibility of the new polypeptide hydrogel was studied by clinical observation and histological study. As a result, a small-molecule polypeptide containing the amino acid RGD sequence (arginine-glycine-aspartic acid) was successfully synthesized, and the polypeptide can be obtained by self-assembly to obtain the injectable RGD polypeptide hydrogel. The RGD polypeptide hydrogel has good biocompatibility in the subconjunctival and anterior chamber of the rabbit. Conclusion The RGD polypeptide hydrogel has good biocompatibility in the conjunctiva and anterior chamber of the rabbit, and has the potential for the application of the sustained-release drug delivery system. The new type of biological material and its controlled-release system will be in the anterior segment of the disease such as glaucoma, iridocyclitis, A role in the treatment of corneal disease. Objective A novel self-assembled polypeptide hydrogel is applied to the conjunctiva of rabbit eye filtering operation, which can reduce the postoperative intraocular pressure (IOP), prolong the survival time of the filtration bubble, and promote the normal healing of the wound after filtration. The purpose of the method is to synthesize the RGD self-assembly The two groups of animal experiments were carried out.1) The subconjunctival injection of the polypeptide hydrogel after the filtration of the rabbit eye line was different. The expression level of connective tissue growth factor (CTGF) mRNA was measured by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). The observation of the slit lamp microscope and the ultrasound biomicroscope (UBM) was performed and the animals were sacrificed after 21 days and the rabbit eyes Histological analysis was performed. The expression level of connective tissue growth factor (CTGF) mRNA and intraocular pressure (IOP) were post-operative 21 days were significantly lower than that in the control group. The function of the bleb and the filter channel is good. The pathological and histological analysis suggests that the RGD polypeptide hydrogel can keep the morphological structure of the bleb and the filter channel after the filtration of the rabbit eye, and reduce the formation of scar. Conclusion The RGD polypeptide hydrogel can decrease the expression level of the connective tissue growth factor (CTGF) mRNA, prolong the survival time of the bleb, and inhibit the formation of the bleeding mark of the filter channel. The internal pressure of the eye was kept low. The RGD polypeptide hydrogel was used to prevent the filtration after the filtration. The purpose of this study is to construct a 5-FU RGD polypeptide hydrogel controlled-release system to study the in vivo release of the controlled-release system. A small-molecule polypeptide containing the RGD sequence (arginine-glycine-aspartic acid) and N-9-bumetacin (FMOC) is synthesized by the method, the RGD polypeptide hydrogel is obtained by self-assembly behavior, and 5 -FU RGD polypeptide hydrogel controlled-release system. In vitro release of a controlled-release system by an altimeter. The 5-FU RGD polypeptide hydrogel was detected by a high performance liquid chromatography (HPLC) chromatograph. A 5-FU RGD polypeptide hydrogel controlled-release system was implanted in the conjunctiva of the rabbit eyes after the line filtration, and the intraocular pressure, slit lamp microscope and other clinical observations were performed on the rabbit eye for different time periods, and different time periods were observed for 3 to 28 days. The results showed that 5-FU was able to release slowly from RGD polypeptide hydrogel controlled-release system. The internal and external drug release was stable, efficient and free of burst. The controlled-release system can make the intraocular pressure (IOP) of the rabbit eyes lower than that of the control group at 28 days after the operation, obviously reduce the toxic and side effect of 5-FU on the surrounding normal eye tissues, The results showed that the filtration function of the bleb and the filter channel was good. The pathological and histological analysis suggested that the RGD polypeptide hydrogel can keep the morphological structure of the bleb and the filter channel after the filtration of the rabbit eye, and obviously reduce the amount of the F-actin. Conclusion 5-FU can be slowly released from the RGD polypeptide hydrogel, and the 5-FU RGD self-assembled polypeptide hydrogel is applied to rabbit eye filtration. The 5-FU RGD polypeptide hydrogel controlled-release system was used to prevent the post-filtration post-filtration.
【学位授予单位】:华中科技大学
【学位级别】:博士
【学位授予年份】:2010
【分类号】:R779.6

【共引文献】

相关期刊论文 前10条

1 朱忠桥;王丽丽;刘蓓;王勇;;氟尿嘧啶联合低分子肝素预防增殖性玻璃体视网膜病变的临床观察[J];第四军医大学学报;2006年15期

2 潘永明;徐国兴;;结缔组织生长因子与眼科疾病关系研究进展[J];福建医药杂志;2006年01期

3 刘艳艳;罗丽卿;吴平;;转化生长因子-β及结缔组织生长因子与翼状胬肉关系的研究现状[J];广东医学院学报;2011年01期

4 黄丽娜;姚晓明;;翼状胬肉成纤维细胞中COX-2的表达及其抑制剂的实验研究(英文)[J];国际眼科杂志;2006年01期

5 王勇;王丽丽;朱忠桥;刘蓓;潘爱珠;黄玲;;氟尿嘧啶联合低分子肝素预防增殖性玻璃体视网膜病变的视网膜电图[J];国际眼科杂志;2006年03期

6 唐卫华;汪昌运;柯美魁;欧阳君;刘云伟;;CTGF在兔眼小梁切除术后滤过泡瘢痕形成中的表达[J];国际眼科杂志;2008年05期

7 向建南;王国华;张海江;霍鸣;;不同的给药途径防治后发性白内障[J];国际眼科杂志;2010年06期

8 胡瑜兰 ,张钧寿;植入剂应用的研究进展[J];国外医药(合成药 生化药 制剂分册);2001年01期

9 罗丽卿;吴平;刘艳艳;何惠娟;王思捷;吴伟全;;CTGF shRNA表达质粒对翼状胬肉成纤维细胞的转染条件优化[J];国际检验医学杂志;2012年01期

10 高华,史伟云,谢立信;药物控释技术以及在眼科的应用[J];国外医学(眼科学分册);2004年05期

相关博士学位论文 前10条

1 陆燕;TGF-β1在TAO眼外肌纤维化中的作用及相关信号传导通路研究[D];第二军医大学;2011年

2 郭长梅;CTGF在增生性玻璃体视网膜病变及视网膜色素上皮细胞中的作用[D];第四军医大学;2004年

3 杨咏梅;角膜创伤愈合中TGF、CTGF的表达及MAPK、Smad信号传导通路的实验研究[D];山东大学;2005年

4 李运;PDLLA/GA抑制青光眼滤过手术后瘢痕形成的实验研究[D];山东大学;2005年

5 李岚;小鼠角膜创伤修复的分子机制[D];青岛大学;2005年

6 刘茂雄;海藻酸钠—环孢霉素A药膜在青光眼滤过性手术中抗增殖作用的实验研究[D];吉林大学;2006年

7 蔡小玲;木瓜凝乳蛋白酶的分离纯化及应用基础研究[D];华南理工大学;2004年

8 安建斌;姜黄素防治增殖性玻璃体视网膜病变的实验研究[D];河北医科大学;2009年

9 张丽;CTGF基因干扰对转化生长因子β_2诱导的人晶状体上皮细胞间质转分化的调控研究[D];浙江大学;2009年

10 田姣;兔眼玻璃体腔药物泵入的初步研究[D];中南大学;2013年

相关硕士学位论文 前10条

1 李坤;肝靶向免疫基因载体的研究[D];郑州大学;2010年

2 许静;汉防己甲素联合5-氟尿嘧啶壳聚糖微球防治实验性PVR的实验研究[D];山东中医药大学;2010年

3 王兴荣;5-氟尿嘧啶聚乳酸微球防治增殖性玻璃体视网膜病变的基础研究[D];山东中医药大学;2009年

4 郝艳君;干扰素联合氟尿嘧啶抑制兔增殖性玻璃体视网膜病变的疗效观察[D];山西医科大学;2011年

5 宋晓瑾;绞股蓝皂甙对人翼状胬肉成纤维细胞增殖的影响[D];华中科技大学;2010年

6 李越;地塞米松—PLGA纳米粒的制备及其兔眼内药物代谢动力学[D];第四军医大学;2005年

7 苏亚丽;三氧化二砷对体外培养的人视网膜色素上皮细胞作用的实验研究[D];郑州大学;2005年

8 滕彦;玻璃体内注射用微球的制备[D];浙江大学;2005年

9 周卫为;针刺分离联合结膜下注射干扰素治疗失败滤过泡的临床研究[D];广西医科大学;2006年

10 栗印兰;硅胶与羊膜植入对青光眼滤过术后碱性成纤维细胞生长因子表达的影响[D];大连医科大学;2006年



本文编号:2440944


论文下载
论文发表
教材专著
专利申请


    下载步骤:
    1.微信扫码,备注编号 2440944.
    2.
    点击下载


    本文链接:http://www.bigengculture.com/yixuelunwen/yank/2440944.html