本文選題：玻璃體填充物 + 0.8%溫敏性羥丁基幾丁糖　； 參考：《第二軍醫(yī)大學(xué)》2017年碩士論文

【摘要】：研究目的:玻璃體可以支撐視網(wǎng)膜,減緩?fù)饬_擊;也可以儲(chǔ)存氧氣、葡萄糖、抗壞血酸等,支持相鄰組織代謝;還可以避免視網(wǎng)膜與眼前段之間的物質(zhì)擴(kuò)散;同時(shí)玻璃體也是眼內(nèi)最大的屈光物質(zhì),一旦損傷即不可再生。發(fā)育異常、組織退變、眼內(nèi)炎癥、眼外傷、眼內(nèi)出血及全身疾病如糖尿病等均可以導(dǎo)致玻璃體發(fā)生病理變化,從而導(dǎo)致患者視力下降甚至失明。玻璃體視網(wǎng)膜疾病可以通過玻璃體切除術(shù)獲得有效治療,術(shù)后常需要填充合適的材料來維持眼球體積,支撐視網(wǎng)膜。水凝膠由于高含水量,優(yōu)良的光學(xué)透明度和流變性能成為了玻璃體填充物研究熱點(diǎn)。本實(shí)驗(yàn)通過體外檢測(cè)溫敏性羥丁基幾丁糖(hydroxybutyl chitosan,HBC)凝膠的光學(xué)性質(zhì)、物理學(xué)性質(zhì)、成膠時(shí)間和急性眼刺激情況,分析溫敏性羥丁基幾丁糖凝膠進(jìn)行玻璃體填充的可行性,并將溫敏性羥丁基幾丁糖填充兔眼玻璃體內(nèi),進(jìn)一步探索其是否適合作為玻璃體填充物。材料和方法:實(shí)驗(yàn)一:溫敏性羥丁基幾丁糖作為玻璃體填充物的基礎(chǔ)性能研究溫敏性羥丁基幾丁糖濃度越高,透明度越差,成膠溫度也越低。其中0.8%溫敏性羥丁基幾丁糖在溶膠及凝膠狀態(tài),均為透明形態(tài),并且適合在37℃成膠,符合人體溫度,可適用于玻璃體內(nèi)填充,所以本實(shí)驗(yàn)選取0.8%溫敏性羥丁基幾丁糖作為實(shí)驗(yàn)材料。(1)、體外測(cè)量0.8%溫敏性羥丁基幾丁糖凝膠含水率、透光率、屈光指數(shù)、比重、酸堿度和存儲(chǔ)模量、損耗模量,與自然玻璃體進(jìn)行比較。(2)反復(fù)測(cè)量并記錄其溶膠轉(zhuǎn)變?yōu)槟z的相變時(shí)間。(3)、將0.1ml、0.3ml的0.8%溫敏性羥丁基幾丁糖分別滴入6只兔眼結(jié)膜囊,72小時(shí)內(nèi)通過裂隙燈觀察結(jié)膜、角膜、虹膜是否有急性炎癥刺激反應(yīng)。實(shí)驗(yàn)二:溫敏性羥丁基幾丁糖填充兔眼玻璃體安全性實(shí)驗(yàn)研究36只白兔隨機(jī)分為三組,右眼為手術(shù)操作眼,進(jìn)行玻璃體切除手術(shù),術(shù)后A組白兔填充溫敏性羥丁基幾丁糖(HBC),B組填充透明質(zhì)酸鈉凝膠,C組填充平衡鹽溶液(BSS)。術(shù)后1、3、7、14、21、28天分別行裂隙燈、直接檢眼鏡檢查術(shù)眼各部位(結(jié)膜、角膜、前房、晶狀體、玻璃體、眼底)情況,眼壓計(jì)測(cè)量眼壓。術(shù)后4周、8周、12周分別行眼部B超、眼底照相及視網(wǎng)膜光學(xué)相干斷層成像等檢查,并隨機(jī)從三組中選取部分實(shí)驗(yàn)動(dòng)物進(jìn)行眼球摘除,制作病理切片,通過光學(xué)顯微鏡和電子顯微鏡觀察超微結(jié)構(gòu)改變。結(jié)果:1、0.8%溫敏性羥丁基幾丁糖凝膠含水率為98.7%、屈光指數(shù)為1.3321、透光率為99.95%、比重為1.008 g/cm3,物理性質(zhì)及光學(xué)性質(zhì)均接近于自然玻璃體,pH值相較于自然玻璃體(7.0~7.5)稍低,為6.97,不排除操作誤差及溫度影響。溫敏性羥丁基幾丁糖凝膠狀態(tài)下儲(chǔ)存能量(彈性)平均值為267.08±0.78 Pa,損耗模量(粘性)平均值為17±1.12Pa,屬于彈性材料。溫敏性羥丁基幾丁糖4℃到37℃相變(溶膠→凝膠)平均用時(shí)為59±2s。將0.8%溫敏性羥丁基幾丁糖滴入實(shí)驗(yàn)動(dòng)物結(jié)膜囊內(nèi)72小時(shí),兔眼穹窿部結(jié)膜可見凝膠殘余物和少許分泌物,未見結(jié)膜充血、角膜損傷、虹膜粘連,兔眼瞳孔對(duì)光反射正常。2、玻璃體切除術(shù)后,A組(溫敏性羥丁基幾丁糖組)、B組(透明質(zhì)酸鈉組)、C組(BSS組)三組白兔均出現(xiàn)了暫時(shí)性眼內(nèi)炎癥反應(yīng),后期發(fā)生晶狀體混濁,其中A組2例(16.7%),B組3例(25%),C組1例(8.3%)。A組眼壓于術(shù)后7天與術(shù)前比較有差異(P0.05),B組眼壓于術(shù)后2月時(shí)降低,與術(shù)前比較有差異(P0.05)。術(shù)后眼后節(jié)檢查可見A組兔眼玻璃體內(nèi)不透明,呈現(xiàn)灰白色團(tuán)塊狀混濁,隨時(shí)間變化團(tuán)塊逐漸變小,眼底模糊無法窺清。B組玻璃體透明度欠佳,眼底細(xì)節(jié)隱約可見。C組玻璃體透明,眼底細(xì)節(jié)清晰可見。組織病理學(xué)顯示三組兔眼角膜及視網(wǎng)膜超微結(jié)構(gòu)未見明顯異常,其中視網(wǎng)膜平伏,結(jié)構(gòu)層次清晰,未發(fā)生視網(wǎng)膜脫離及增生,但B組兔眼視網(wǎng)膜神經(jīng)節(jié)細(xì)胞層細(xì)胞有所減少。結(jié)論:1、0.8%溫敏性羥丁基幾丁糖凝膠的光學(xué)性質(zhì)和物理性質(zhì)及粘彈性可以模擬自然玻璃體。2、0.8%溫敏性羥丁基幾丁糖填充兔眼玻璃體顯示出良好生物相容性,但是會(huì)引起玻璃體的不透明和灰白色團(tuán)塊狀混濁,目前尚不是理想的玻璃體替代物。玻璃體內(nèi)水凝膠藥物遞送系統(tǒng)通常僅占據(jù)玻璃體腔的一小部分,它們并不一定要求眼內(nèi)呈透明狀,溫敏性羥丁基幾丁糖在玻璃體內(nèi)藥物遞送系統(tǒng)中可有進(jìn)一步研究。
[Abstract]:Objective: the vitreous body can support the retina, slow down the external force impact, and can also store oxygen, glucose, ascorbic acid, support metabolism of adjacent tissues, and avoid the material diffusion between the retina and the anterior segment; and the vitreous body is also the largest diopter in the eye. Once the injury is nonrenewable, abnormal development, tissue degeneration, Intraocular inflammation, ocular trauma, intraocular bleeding, and systemic diseases such as diabetes can cause pathological changes in the vitreous body, which can lead to visual loss and even blindness. Vitreous retinal diseases can be effectively treated by vitrectomy, and the appropriate materials are often needed to maintain the volume of the eyeball and support the retina. The excellent optical transparency and rheological properties of hydrogels have become a hot spot in the study of vitreous padding. In this experiment, the optical properties, physical properties, gelation time and acute eye stimulation of thermosensitive hydroxybutyl chitosan (hydroxybutyl chitosan, HBC) gels were detected in this experiment. The feasibility of filling the vitreous body with the glue and filling the glass body of the rabbit eye with thermosensitive hydroxybutyl chitosan to further explore whether it is suitable as a vitreous filler. Materials and methods: Experiment 1: the temperature sensitive hydroxybutyl chitosan as the base of the vitreous filler, the higher the temperature sensitive hydroxybutyl chitosan concentration, the transparency. The more poor the gelatin temperature is, the 0.8% thermosensitive hydroxybutyl chitosan is transparent in the sol and gel state, and is suitable for filling in the body at 37 degrees centigrade, which is suitable for the body temperature. So 0.8% thermosensitive hydroxybutyl chitosan is selected as the experimental material in this experiment. (1) the measurement of 0.8% thermosensitive hydroxyl butyl in vitro Water content, transmittance, refractive index, diopter index, specific gravity, pH, storage modulus, loss modulus, and natural vitreous modulus were compared with natural vitreous. (2) the phase transition time of the sol changed into gel was measured and recorded repeatedly. (3) 0.1ml, 0.3ml 0.8% thermosensitive hydroxybutyl chitosan was dripped into 6 rabbit eye conjunctiva, and the slit lamp was observed within 72 hours. Experimental two: 36 rabbits were randomly divided into three groups: the right eye was operated in three groups, the right eye was operated in the eye, the vitrectomy was performed, the white rabbits in the A group were filled with thermosensitive hydroxyl chitosan (HBC), and the B group filled with sodium hyaluronate. The gel, C group filled the balance salt solution (BSS). After 1,3,7,14,21,28 days, the eyes were examined by the fissure lamp, and the ophthalmoscope was examined by direct ophthalmoscope (conjunctiva, cornea, anterior chamber, lens, vitreous body, fundus), and intraocular pressure was measured by the intraocular pressure meter. 4 weeks, 8 weeks, and 12 weeks after operation, the eye B ultrasound, fundus photography and retina optical coherence tomography were performed respectively. Some experimental animals were extirpated from the three groups, and the pathological sections were made. The ultrastructural changes were observed by optical microscope and electron microscope. Results: the moisture content of 1,0.8% thermosensitive hydroxyl butyl chitosan gel was 98.7%, the refractive index was 1.3321, the transmittance was 99.95%, the specific gravity was 1.008 g/cm3, and the physical and optical properties were all Close to the natural vitreous body, the pH value is slightly lower than that of the natural vitreous body (7.0~7.5), which is slightly lower than the natural vitreous body (7.0~7.5), and is 6.97. It does not exclude the operating error and temperature. The average value of the storage energy (elasticity) is 267.08 + 0.78 Pa, the average value of the loss modulus (stickiness) is 17 + 1.12Pa, and the temperature sensitive hydroxybutyl chitosan is 4 centigrade. The average use of phase transition (sol-gel) at 37 degrees (sol-gel) was 59 + 2s. to drop 0.8% thermosensitive hydroxybutyl chitosan into the conjunctival sac for 72 hours. The conjunctiva of the rabbit eye dome could see the gel remnants and a few secretions. No conjunctiva congestion, corneal injury, iris adhesion, rabbit eye pupil to light reflex normal.2, vitrectomy, A group (Wen Min) In group B (sodium hyaluronate group), group B (sodium hyaluronate group) and group C (group BSS), there were temporary intraocular inflammatory reactions in group C (group BSS), and late lens opacities occurred in group A, group B (16.7%), group B, 3 (25%), 1 group (8.3%) in group C (P0.05) compared with pre operation (P0.05), and group B decreased in February, compared with pre operation. There was a difference (P0.05). The posterior segment of the eye showed that the vitreous body of the rabbit eyes of group A was opaque and showed a gray and white lump of turbid. The changes of the masses gradually became smaller with time. The blur of the fundus could not be seen in the vitreous body of the group.B, the vitreous body of the.C group was clear and the details of the fundus were clearly visible. The histopathology showed three groups of rabbits' eyes. There were no obvious abnormalities in the ultrastructure of the cornea and retina, of which the retina was flat, the structure was clear, retinal detachment and proliferation did not occur, but the retinal ganglion cell layer cells in the B group were reduced. Conclusion: the optical and physical properties and viscoelasticity of the 1,0.8% thermosensitive hydroxyl butyl chitosan gel can simulate the natural vitreous body. 2,0.8% thermosensitive hydroxyl butyl chitosan has good biocompatibility in vitreous body, but it can cause opaque and gray white turbid in vitreous. It is not an ideal substitute for vitreous body. The glass body hydrogel delivery system usually only occupies a small part of the glass body cavity. They are not necessarily required. The eye is transparent and thermosensitive butyl chitin can be further studied in vitreous drug delivery system.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R779.6

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