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
[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】
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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
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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
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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
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