不同基质眼膏注入豚鼠眼睑和泪囊周围的不良反应和治疗

发布时间：2018-06-12 08:55

本文选题：不同基质眼膏 + 眼睑和泪囊　；参考：《郑州大学》2010年硕士论文

【摘要】： 目的眼膏常用于眼表、眼前节病变和眼科手术后,优点是能维持结膜囊内长时间有效的药物浓度,减少用药次数,防治药物流失。近年来,文献中诸多报道泪道探通或激光疏通术后,注入眼膏以防止泪道再次粘连,可起到良好的软性支撑作用。但在临床工作中也见到一些患者,眼膏通过假道进入泪囊周围和眼睑组织,进而在眶组织内降解吸收,引起严重的炎症反应,且治疗困难。本实验目的：观察外用眼膏进入眼睑和泪囊周围组织内的不良反应情况；进而寻求有效地治疗方法。为由于眼膏进入眼部组织内造成的炎症反应的治疗提供实验依据。第一部分：使用以凡士林和羊毛脂为基质的红霉素眼膏、以玻璃酸钠为基质的氧氟沙星眼膏,以及甲基纤维素,分别注射到豚鼠眼睑皮下和泪囊周围,建立动物模型,观察和比较不同基质眼膏在豚鼠眼睑皮下、泪囊周围的不良反应；第二部分：筛选眼膏进入眼睑周围组织内的有效治疗方法。材料与方法动物与分组选用出生两周龄的健康清洁级豚鼠72只(郑州大学实验动物中心提供),雌雄不限,年龄2～4周,体重120g～150g,排除各种眼科疾患。眼周为白色为宜,以便于大体观察。随机分为A、B、C组,每组24只。动物模型制作动物以速眠新0.1ml/kg进行腹腔麻醉。剪去下眼睑及周围毛发,暴露皮肤,吉尔碘消毒。在显微镜下下睑缘下3mm进注射液深度2mm。A组右眼睑轮匝肌及泪囊周围注射以凡士林和羊毛脂为基质的红霉素眼膏0.5ml,B组右眼睑轮匝肌及泪囊周围注射以玻璃酸钠为基质的氧氟沙星眼膏0.5ml,C组作为对照组右眼睑轮匝肌及泪囊周围注射甲基纤维素0.5ml。0.5ml的药物剂量可在下睑形成直径约15mm的皮丘。观察项目与时间点分别在注射后1天、3天、7天、14天、21天、28天六个时间点进行观察。观察1、3、7天的充血肿胀程度,直径小于10mm为Ⅰ红肿,10～15mm为Ⅱ°红肿,大于15mm以上为Ⅲ°红肿；六个时间点的局部结节形成情况和眼膏降解吸收情况,取组织标本做切片HE染色,观察各时间点的局部组织病理学变化。统计学分析处理应用SPSS10.0统计软件包,三组间红肿肿胀程度的有序变量资料比较采用秩和检验,结节形成情况和眼膏降解吸收情况的计量资料比较采用单因素方差分析。结果炎症反应情况A组：第1天可见严重的炎症反应,均为Ⅲ°红肿,甚至坏死形成溃疡；第3天充血肿胀减轻,Ⅲ°红肿仍有17眼；7天16只眼为Ⅰ°红肿。B组：第1天充血肿胀,23眼为Ⅱ°红肿,1眼为Ⅰ°红肿；3天后消退。C组第1天24眼均为Ⅰ°红肿,3天后完全消退。A组各时间点与B组、C组比较,差异有统计学意义(P＜0.05)。局部结节形成情况A组：第1天结节形成明显,随时间直径逐渐缩小,但持续观察28天仍不见消退。B组：1天可见结节,3天消退。C组第1天没有有结节形成。A组各时间结节直径与B组、C组比较,差异有统计学意义(P＜0.05)。眼膏降解吸收情况A组第1天切开皮肤后可见降解吸收不明显,大于注射时15mm,7天后逐渐被纤维组织包裹。B组第1天,直径小于注射时的15mm,3天后全部吸收。C组第1天全部吸收。A组各时间点与B组、C组比较,眼膏的降解吸收吸收差异有统计学意义(P＜0.05)。组织病理改变A组以羊毛脂和凡士林为基质的眼膏进入组织后,组织病理学可见炎症反应剧烈,早期以中性粒细胞为主的各种炎症细胞浸润,中晚期淋巴细胞和异物巨细胞增多,纤维组织增生,眼膏降解吸收缓慢。B组以玻璃酸钠为基质的眼膏进入组织后组织反应轻,早期少量炎症细胞浸润,3天后降解吸收,未见明显的纤维组织增生。C组甲基纤维素注入组织后,仅少量炎症细胞浸润,3天组织结构恢复正常。结论以羊毛脂和凡士林为基质的眼膏进入眼睑和泪囊周围组织中,将引起严重的组织炎症反应,可有纤维包裹形成,但降解吸收极慢,需积极给予治疗。以玻璃酸钠为基质的眼膏仅引起轻度组织炎症反应,3天左右降解吸收,无明显增生病变。无需特殊治疗。甲基纤维素组的组织反应轻微,24小时可降解吸收,无明显炎症。无需治疗。材料与方法动物与分组健康清洁级豚鼠48只,4周龄,随机分为A、B、C三组,每组16只。动物模型制作动物以速眠新0.1ml/kg进行腹腔麻醉。剪去下眼睑及周围毛发,暴露皮肤,吉尔碘消毒。在各组豚鼠右眼睑轮匝肌及泪囊周围注射以凡士林和羊毛脂为基质的红霉素眼膏0.5ml。在下睑形成直径15mm皮丘。治疗方法A组于注射后24小时局部注射地塞米松5mg和庆大霉素注射液4万单位共2ml；B组注射后24小时局部切开清除眼膏后生理盐水冲洗；C组注射后24小时局部切开清除眼膏加生理盐水冲洗后,局部注射地塞米松5mg和庆大霉素注射液4万单位共2ml。观察项目与时间点观察治疗后1、3、7天观察充血肿胀情况,直径小于10mm为Ⅰ°红肿,10～15mm为Ⅱ°红肿,大于15mm以上为Ⅲ°红肿；1、3、7、14天结节形成情况。A、B、C三组各时间点随机处死四只豚鼠,取组织标本做切片HE染色,观察各时间点的局部组织病理学变化。统计学分析处理应用SPSS10.0统计软件包,三组间充血肿胀况的有序变量资料采用秩和检验,结节形成情况的计量资料采用单因素方差分析。取α=0.05为检验水准。结果三组充血肿胀比较A组第1天14眼为Ⅲ°红肿。第3天充血红肿减轻,Ⅲ°红肿仍有9眼,7天8只眼均为Ⅰ°红肿。B第1天充血肿胀,15眼为Ⅲ°红肿,1眼Ⅱ°红肿,7天8只眼均为Ⅰ°红肿。C组第1天13眼为Ⅲ°红肿,3天5只眼Ⅱ°红肿,7天红肿消退。C组第七天与其他两组比较有统计学意义(P＜0.05)。三组结节形成情况比较A、B、C三组各时间点均有明显的结节形成,随观察时间点消退不明显。三组各时间点比较无统计学意义(P0.05)。组织病理学A组炎症细胞浸润,眼膏不能吸收,炎症反应和纤维组织增生仍然明显。B组组织内未见眼膏,仍有明显的炎症细胞浸润和纤维组织形成。C组未见眼膏残留,炎症细胞浸润少,恢复快,但纤维组织增生明显,局部形成瘢痕。结论以羊毛脂和凡士林为基质的眼膏进入眼睑和泪囊周围组织后,采用局部切开清除眼膏,生理盐水冲洗后,再局部注射地塞米松和庆大霉素,是效果最好的治疗方法。
[Abstract]:objective
Eye ointment is often used in ocular surface, anterior segment lesion and eye surgery. The advantage is to maintain a long and effective drug concentration in the conjunctival capsule, reduce the number of drugs and prevent the loss of drugs. In recent years, many reports have reported that after lacrimal passage exploration or laser dredging, the eye ointment is injected to prevent the re adhesion of lacrimal duct, and it can play a good soft support. But in clinical work, some patients are also seen. Eye ointment enters the lacrimal sac and eyelid tissue through a false path, and then degrades and absorbs in the orbital tissue and causes severe inflammatory reactions, and the treatment is difficult.
Objective: To observe the adverse reaction of the external eye ointment into the eyelid and the surrounding tissue of the lacrimal sac, and to seek effective treatment. The first part: the use of Erythromycin Eye Ointment with vaseline and sheep hair fat as the basis for the treatment of the eye ointment. Sodium acid - based Ofloxacin Eye Ointment, and methyl cellulose, were injected into the subcutaneous and lacrimal sac of the guinea pig's eyelids, and animal models were established to observe and compare the adverse reactions of different matrix eye ointments in guinea pig eyelids and around the lacrimal sac. The second part: the effective treatment method of screening eye ointment into the surrounding eyelid tissue. Method
Animals and groups selected 72 healthy and clean grade guinea pigs of two weeks of age (provided by experimental animal center of Zhengzhou University), male and female, age 2~4 weeks, weight 120g to 150g, excluding all kinds of ophthalmological disorders. The eye week is white, which is convenient for general observation. It is randomly divided into A, B, C group, 24 rats in each group.
Animal model animals made abdominal anesthesia with fast sleeping 0.1ml/kg. Cut off the lower eyelids and the surrounding hair, expose the skin, and disinfect Gil iodine. In the lower lid edge of the lower eyelid, 3mm injection deep 2mm.A group and the right eyelid muscle and the lacrimal sac were injected with vaseline and lanolin as the matrix of Erythromycin Eye Ointment 0.5ml, B group right eyelid muscle And the injection of sodium hyaluronate as the matrix of Ofloxacin Eye Ointment 0.5ml around the lacrimal sac, group C as the control group the dose of the right eye palpebral orbicularis muscle and the injection of methyl cellulose 0.5ml.0.5ml around the dacryocyst could form the lower eyelid with a diameter of about 15mm in the lower eyelid.
Observation items and time points were observed at 1 days, 3 days, 7 days, 14 days, 21 days, 28 days, and six time points were observed. The degree of congestion and swelling of 1,3,7 days was observed, the diameter was less than 10mm I red swelling, 10 to 15mm was second degree red and swollen, more than 15mm was third degree red and swelling, the formation of local nodules and the degradation and absorption of eye ointment at six time points were taken. Tissue specimens were stained with HE staining to observe the local histopathological changes at different time points.
SPSS10.0 statistical software package was used for statistical analysis. The rank sum test of the swelling degree of the three groups was compared with the rank sum test, the formation of nodules and the measurement data of the degradation and absorption of eye ointment were compared by single factor analysis of variance.
Inflammatory response group A: first days of severe inflammatory reaction, all were III degree red swelling, and even necrosis formed ulcers; third days, congestion and swelling were alleviated, 17 eyes were red and swollen in 7 days, 16 eyes were I degree red and swollen.B group, 23 eyes were second degree red swelling, 1 eyes were I degree red swelling, and 3 days after first days of first days and first eyes were I degree red swelling, After 3 days, the.A group disappeared completely. Compared with group B and group C, the difference was statistically significant (P < 0.05).
The formation of local nodules in group A: first days of nodule formation was obvious, with time diameter gradually narrowing, but continued observation for 28 days was still not seen in group.B: 1 days of nodules were seen, and 3 days of regression of.C group had no nodular formation in group.A with B group, and C group compared with group C (P < 0.05).
The degradation and absorption of eye ointment in the A group was not obvious after first days of incision of the skin, which was more than 15mm at the time of injection. After 7 days, the.B group was gradually wrapped by fibrous tissue for first days, the diameter was less than the 15mm at the injection, and all of the.C groups absorbed all the.A group for first days after 3 days, and all the time points of the group of.A were compared with the B group. The difference of the degradation absorption and absorption of the eye ointment was statistically significant compared with that of the C group. Significance (P < 0.05).
Histopathological changes in A group with Lanolin and vaseline based ointment entered the tissue, histopathology showed severe inflammatory reaction, early neutrophil based inflammatory cells, intermediate and advanced lymphocyte and foreign body giant cells, fibrous tissue hyperplasia, and slow.B group with sodium hyaluronate as matrix. After the eye ointment entered the tissue, the tissue reaction was light and a small amount of inflammatory cells were infiltrated in the early stage. After 3 days, the tissue was degraded and absorbed. No obvious fibrous hyperplasia.C group was injected into the tissue, only a small amount of inflammatory cells were infiltrated, and the histological structure returned to normal on the 3 day.
The eye ointment based on lanolin and vaseline into the eyelid and the surrounding tissue of the lacrimal sac will cause serious tissue inflammation and can be formed by fibrous encapsulation, but the degradation and absorption are very slow and need to be treated actively.
The ointment made of sodium hyaluronate only caused mild tissue inflammatory reaction, and absorbed and absorbed 3 days. There was no obvious hyperplasia. No special treatment was needed.
The methylcellulose group had mild tissue reaction and could be absorbed and absorbed for 24 hours without obvious inflammation. No need for treatment. Materials and methods.
48 healthy and clean guinea pigs, 4 weeks old, were randomly divided into A, B and C three groups, 16 in each group.
Animal model animals were anesthetized with fast sleeping 0.1ml/kg. Cut off the lower eyelids and the surrounding hair, expose the skin, and disinfect Gil iodine. In each group of guinea pigs, the right eyelid muscles and lacrimal sac were injected with vaseline and lanolin as the matrix of Erythromycin Eye Ointment 0.5ml. in the lower eyelid diameter 15mm mound.
In group A, 24 hours after injection of dexamethasone 5mg and 40 thousand units of gentamicin injection, 40 thousand units of 2ml were injected, and group B was partially cut to clear the eye ointment after 24 hours of injection, and the local incision of eye ointment and saline irrigation after injection of C after injection in group C, local injection of dexamethasone 5mg and gentamicin injection 4 Ten thousand units 2ml.
Observation items and time point observation after 1,3,7 days after 1,3,7 days to observe the congestion and swelling, diameter less than 10mm is I degree red swelling, 10 to 15mm is second degree red swelling, more than 15mm is third degree red swelling, 1,3,7,14 day nodule formation of.A, B, C three groups at random to kill four guinea pigs, biopsy specimens for HE staining, observe the local point of the local point Histopathological changes.
SPSS10.0 statistical software package was used for statistical analysis. The ordered variable data of three groups of hematoma expansion were tested by rank sum test. The measurement data of nodular formation were analyzed by single factor variance. The results of alpha =0.05 were tested.
The swelling and swelling of the three groups in the first days of the three groups was III degree red and swelling, third days of red swelling and swelling were alleviated, 9 eyes were red and swollen in third days, 8 eyes were red swelling, first days, 15 eyes were red swelling, 1 eyes were red and swollen in 1 eyes, and 14 eyes in group I was I degree red and swollen on the 7 days in group I of.C There was a statistically significant difference between the two groups (P < 0.05).
The formation of three groups of nodules was compared with A, B, and C three groups with obvious nodule formation at each time point, and the regression was not obvious with the observation time point. There was no significant difference between the three groups at each time point (P0.05).
Histopathology A group inflammatory cell infiltration, eye ointment can not absorb, inflammatory reaction and fibrous tissue proliferation still obviously no eye ointment in group.B, still obvious inflammatory cell infiltration and fibrous tissue formation of.C group no eye ointment residue, inflammatory cell infiltration less, rapid recovery, but fibrous tissue hyperplasia, local scar formation.
After the eye ointment based on lanolin and vaseline enters the eyelid and the tissue around the lacrimal sac, the local incision is used to clear the eye ointment. After the saline irrigation, the local injection of dexamethasone and gentamicin is the best therapeutic method.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R779.6

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