不同基質(zhì)眼膏進入豚鼠眼眶的不良反應
發(fā)布時間：2018-08-25 07:50
【摘要】：眼膏是眼科藥物的常用劑型,具有在結(jié)膜囊內(nèi)滯留時間長,能減輕眼瞼對眼球摩擦等優(yōu)點,但通過手術(shù)創(chuàng)口、淚道探通創(chuàng)口或者假道進入眼瞼皮下、結(jié)膜下或眼眶軟組織內(nèi),可引起嚴重的組織反應。臨床上遇到多起淚道探通或淚道激光疏通治療后,注入的眼膏進入眼瞼或眼眶組織中,以及耳鼻喉科手術(shù)后填塞凡士林紗條,引起嚴重眶內(nèi)組織反應的病例。 本實驗是將以凡士林、羊毛脂和液體石蠟為基質(zhì)的紅霉素眼膏和以玻璃酸鈉和卡波姆為基質(zhì)的氧氟沙星眼膏以及羥丙基甲基纖維素分別注入眼眶,建立不同基質(zhì)眼膏進入眼眶軟組織的動物模型,觀察和比較進入眼眶軟組織的不良反應。 材料與方法 動物與分組健康清潔級豚鼠63只(鄭州大學實驗動物中心提供),雌雄不限,年齡1-2周,體重100g-140 g,排除各種眼科疾患。以眼周淺色為宜,便于大體觀察。63只豚鼠隨機分為A、B、C組,每組21組。 動物模型制作消毒眼瞼周圍皮膚,使用10%的水合氯醛0.3g/k腹腔內(nèi)注射誘導全麻。用1 ml注射器22 G針頭從眶下緣的外1/3與內(nèi)2/3交界處皮膚進針達眼球后,注入以凡士林、液體石蠟和羊毛脂為紅霉素眼膏(A組)、以玻璃酸鈉和卡波姆為基質(zhì)的氧氟沙星眼膏(B組)、羥丙基甲基纖維素(C組)各0.3ml,正常對照眼不做處理。 觀察項目和時間點分別在注射后2 h、1 d、3 d、7 d、14 d、21d、28 d七個時間點進行觀察。記錄眼部紅腫、腫脹情況、眼球突出情況、球后阻力等炎癥反應情況。每時間點每組隨機處死3只豚鼠,觀察大體標本上眼膏在眶內(nèi)的擴散情況、HE染色組織病理學變化。 統(tǒng)計學分析處理應用SPSS17.0統(tǒng)計軟件包,3組間炎癥反應的有序變量資料比較采用秩和檢驗,取α=0.05為檢驗水準。 結(jié)果 A組早期結(jié)膜腫脹、眼球突出,球后阻力增加最為嚴重,持續(xù)時間最長,病理早期以中性粒細胞為主的炎癥細胞浸潤及晚期可見成纖維細胞增生包裹,晚期可見成纖維細胞增生,異物肉芽腫形成,炎癥浸潤和細胞增殖反應最重。 B組早期炎癥反應重,以中性粒細胞和嗜酸性粒細胞為主的炎癥細胞浸潤,且炎細胞數(shù)目明顯多于A組,但未見成纖維細胞增生。 C組注射后眶組織充血水腫消失快,炎癥細胞最少,未見纖維組織增生。 注射后3d各組間差異均有統(tǒng)計學意義(H=9.089,H=16.830,H=17.084,P均0.05)。 結(jié)論 以凡士林、羊毛脂和液狀石蠟為基質(zhì)的眼膏進入豚鼠眶軟組織后,引起的組織炎癥反應最重,局部纖維組織增生,形成異物肉芽腫,降解所需時間較長。 以玻璃酸鈉和卡波姆為基質(zhì)的眼膏進豚鼠眶軟組織后,3d內(nèi)可降解、吸收,局部無纖維組織增生。 羥丙基甲基纖維素引起的局部炎癥反應最輕,24 h內(nèi)可完全降解、吸收,無纖維組織增生。
[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 偽 -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.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2011
【分類號】：R77
本文編號：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 偽 -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.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2011
【分類號】：R77
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