不同基质眼膏进入豚鼠眼眶的不良反应
发布时间：2018-08-25 07:50
【摘要】：眼膏是眼科药物的常用剂型,具有在结膜囊内滞留时间长,能减轻眼睑对眼球摩擦等优点,但通过手术创口、泪道探通创口或者假道进入眼睑皮下、结膜下或眼眶软组织内,可引起严重的组织反应。临床上遇到多起泪道探通或泪道激光疏通治疗后,注入的眼膏进入眼睑或眼眶组织中,以及耳鼻喉科手术后填塞凡士林纱条,引起严重眶内组织反应的病例。 本实验是将以凡士林、羊毛脂和液体石蜡为基质的红霉素眼膏和以玻璃酸钠和卡波姆为基质的氧氟沙星眼膏以及羟丙基甲基纤维素分别注入眼眶,建立不同基质眼膏进入眼眶软组织的动物模型,观察和比较进入眼眶软组织的不良反应。 材料与方法 动物与分组健康清洁级豚鼠63只(郑州大学实验动物中心提供),雌雄不限,年龄1-2周,体重100g-140 g,排除各种眼科疾患。以眼周浅色为宜,便于大体观察。63只豚鼠随机分为A、B、C组,每组21组。 动物模型制作消毒眼睑周围皮肤,使用10%的水合氯醛0.3g/k腹腔内注射诱导全麻。用1 ml注射器22 G针头从眶下缘的外1/3与内2/3交界处皮肤进针达眼球后,注入以凡士林、液体石蜡和羊毛脂为红霉素眼膏(A组)、以玻璃酸钠和卡波姆为基质的氧氟沙星眼膏(B组)、羟丙基甲基纤维素(C组)各0.3ml,正常对照眼不做处理。 观察项目和时间点分别在注射后2 h、1 d、3 d、7 d、14 d、21d、28 d七个时间点进行观察。记录眼部红肿、肿胀情况、眼球突出情况、球后阻力等炎症反应情况。每时间点每组随机处死3只豚鼠,观察大体标本上眼膏在眶内的扩散情况、HE染色组织病理学变化。 统计学分析处理应用SPSS17.0统计软件包,3组间炎症反应的有序变量资料比较采用秩和检验,取α=0.05为检验水准。 结果 A组早期结膜肿胀、眼球突出,球后阻力增加最为严重,持续时间最长,病理早期以中性粒细胞为主的炎症细胞浸润及晚期可见成纤维细胞增生包裹,晚期可见成纤维细胞增生,异物肉芽肿形成,炎症浸润和细胞增殖反应最重。 B组早期炎症反应重,以中性粒细胞和嗜酸性粒细胞为主的炎症细胞浸润,且炎细胞数目明显多于A组,但未见成纤维细胞增生。 C组注射后眶组织充血水肿消失快,炎症细胞最少,未见纤维组织增生。 注射后3d各组间差异均有统计学意义(H=9.089,H=16.830,H=17.084,P均0.05)。 结论 以凡士林、羊毛脂和液状石蜡为基质的眼膏进入豚鼠眶软组织后,引起的组织炎症反应最重,局部纤维组织增生,形成异物肉芽肿,降解所需时间较长。 以玻璃酸钠和卡波姆为基质的眼膏进豚鼠眶软组织后,3d内可降解、吸收,局部无纤维组织增生。 羟丙基甲基纤维素引起的局部炎症反应最轻,24 h内可完全降解、吸收,无纤维组织增生。
[Abstract]:Eye ointment is a commonly used dosage form of ophthalmic drugs. It has the advantages of long stay time in conjunctival sac and can reduce the eyelid to eyeball friction. But through the operation wound, lacrimal duct probing the wound or false passage into the eyelid, subconjunctival or orbital soft tissue, etc. Can cause severe tissue reactions. There were many cases of lacrimal duct exploration or lacrimal duct laser therapy, the injected ointment entered the eyelid or orbital tissue, and the vaseline gauze was filled after the operation of otolaryngology, which caused serious intraorbital tissue reaction. In this experiment, erythromycin eye ointment based on vaseline, lanolin and liquid paraffin, ofloxacin eye ointment based on sodium hyaluronate and carbomer and hydroxypropyl methyl cellulose were injected into orbit, respectively. The animal model of different matrix ointment entering orbital soft tissue was established to observe and compare the adverse reaction of entering orbital soft tissue. Materials and methods Sixty-three healthy clean grade guinea pigs (provided by Experimental Animal Center, Zhengzhou University), aged 1-2 weeks, weight 100g-140 g, were excluded from all kinds of ophthalmic diseases. 63 guinea pigs were randomly divided into two groups: group A (n = 21) and group C (n = 21). The skin around eyelid was disinfected with 10% chloral hydrate 0.3g/k intraperitoneally to induce general anesthesia. A 22G needle was injected into the eyeball with a 22 G needle from the outer third of the inferior orbital margin to the inner 2 / 3 of the eye, and vaseline was injected into the eyeball. Liquid paraffin and lanolin were erythromycin eye ointment (group A), ofloxacin eye ointment (group B) with sodium hyaluronate and carbomer as matrix, hydroxypropyl methyl cellulose (group C) as 0.3 ml respectively. The observation items and time points were observed at 2 h, 1 d, 3 d, 7 d, 14 d, 21 d and 28 d, respectively. Record inflammatory reactions such as swelling, exophthalmos, retrobulbar resistance and so on. At each time point, 3 guinea pigs were randomly killed in each group to observe the diffusion of the ointment in the orbit and the histopathological changes of HE staining. SPSS17.0 statistical software package was used to analyze the order variables of inflammatory reaction in the three groups. The rank sum test was used to compare the data, and 伪 -0. 05 was taken as the test level. Results in group A, the early conjunctiva swelling, exophthalmos and retrobulbar resistance increased most seriously and lasted for the longest time. The infiltration of inflammatory cells with neutrophil in the early stage and fibroblast proliferation in the late stage were observed in group A. Fibroblast proliferation, granuloma formation, inflammatory infiltration and cell proliferation were observed in the late stage. In group B, the early inflammatory reaction was severe, and the inflammatory cell infiltration was dominated by neutrophil and eosinophilic granulocyte. The number of inflammatory cells was significantly more than that of group A, but no fibroblast proliferation was found in group C. in group C, hyperemia and edema disappeared quickly, inflammatory cells were the least, and fibrous tissue proliferation was not seen in group C. Three days after injection, there were significant differences among the three groups (P 0.05). Conclusion when the ointment with vaseline, lanolin and liquid paraffin as the base, the inflammation is the most serious, the local fibrous tissue proliferates, the foreign body granuloma is formed, and the degradation time is longer. The eye ointment based on sodium hyaluronate and carbomer could be degraded and absorbed in the orbital soft tissue of guinea pig within 3 days, and the local fibrous tissue could proliferate. The local inflammatory reaction induced by hydroxypropyl methylcellulose could be completely degraded, absorbed and no fibrous tissue proliferated within 24 h.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R77
本文编号：2202241
[Abstract]:Eye ointment is a commonly used dosage form of ophthalmic drugs. It has the advantages of long stay time in conjunctival sac and can reduce the eyelid to eyeball friction. But through the operation wound, lacrimal duct probing the wound or false passage into the eyelid, subconjunctival or orbital soft tissue, etc. Can cause severe tissue reactions. There were many cases of lacrimal duct exploration or lacrimal duct laser therapy, the injected ointment entered the eyelid or orbital tissue, and the vaseline gauze was filled after the operation of otolaryngology, which caused serious intraorbital tissue reaction. In this experiment, erythromycin eye ointment based on vaseline, lanolin and liquid paraffin, ofloxacin eye ointment based on sodium hyaluronate and carbomer and hydroxypropyl methyl cellulose were injected into orbit, respectively. The animal model of different matrix ointment entering orbital soft tissue was established to observe and compare the adverse reaction of entering orbital soft tissue. Materials and methods Sixty-three healthy clean grade guinea pigs (provided by Experimental Animal Center, Zhengzhou University), aged 1-2 weeks, weight 100g-140 g, were excluded from all kinds of ophthalmic diseases. 63 guinea pigs were randomly divided into two groups: group A (n = 21) and group C (n = 21). The skin around eyelid was disinfected with 10% chloral hydrate 0.3g/k intraperitoneally to induce general anesthesia. A 22G needle was injected into the eyeball with a 22 G needle from the outer third of the inferior orbital margin to the inner 2 / 3 of the eye, and vaseline was injected into the eyeball. Liquid paraffin and lanolin were erythromycin eye ointment (group A), ofloxacin eye ointment (group B) with sodium hyaluronate and carbomer as matrix, hydroxypropyl methyl cellulose (group C) as 0.3 ml respectively. The observation items and time points were observed at 2 h, 1 d, 3 d, 7 d, 14 d, 21 d and 28 d, respectively. Record inflammatory reactions such as swelling, exophthalmos, retrobulbar resistance and so on. At each time point, 3 guinea pigs were randomly killed in each group to observe the diffusion of the ointment in the orbit and the histopathological changes of HE staining. SPSS17.0 statistical software package was used to analyze the order variables of inflammatory reaction in the three groups. The rank sum test was used to compare the data, and 伪 -0. 05 was taken as the test level. Results in group A, the early conjunctiva swelling, exophthalmos and retrobulbar resistance increased most seriously and lasted for the longest time. The infiltration of inflammatory cells with neutrophil in the early stage and fibroblast proliferation in the late stage were observed in group A. Fibroblast proliferation, granuloma formation, inflammatory infiltration and cell proliferation were observed in the late stage. In group B, the early inflammatory reaction was severe, and the inflammatory cell infiltration was dominated by neutrophil and eosinophilic granulocyte. The number of inflammatory cells was significantly more than that of group A, but no fibroblast proliferation was found in group C. in group C, hyperemia and edema disappeared quickly, inflammatory cells were the least, and fibrous tissue proliferation was not seen in group C. Three days after injection, there were significant differences among the three groups (P 0.05). Conclusion when the ointment with vaseline, lanolin and liquid paraffin as the base, the inflammation is the most serious, the local fibrous tissue proliferates, the foreign body granuloma is formed, and the degradation time is longer. The eye ointment based on sodium hyaluronate and carbomer could be degraded and absorbed in the orbital soft tissue of guinea pig within 3 days, and the local fibrous tissue could proliferate. The local inflammatory reaction induced by hydroxypropyl methylcellulose could be completely degraded, absorbed and no fibrous tissue proliferated within 24 h.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R77
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