糜玲,周波,李永,彭金刚,汤磊,黄家宇
MI Ling,ZHOU Bo,LI Yong,PENG Jingang,TANG Lei,HUANG Jiayu

• 1:贵州医科大学药学院药物分析教研室
• 2:贵州省化学合成药物研发利用工程技术研究中心
• 3:贵州医科大学

摘要(Abstract)：

目的:探讨不同构型吉法酯对东莨菪碱氢溴酸盐所致干眼症大鼠角膜的保护作用。方法:40只雌性Wistar大鼠,均分为正常组、生理盐水对照组、4Z吉法酯治疗组(4Z组)、4E吉法酯治疗组(4E组)和混合吉法酯治疗组(混合组),后4组大鼠采用皮下注射东莨菪碱氢溴酸盐联合风扇制备干眼症大鼠模型,正常组和生理盐水组大鼠用生理盐水滴眼、其余各治疗组分别使用10 g/L的各构型吉法酯滴眼液连续治疗14 d;于造模前、治疗第7及14天采用Shirmer I试验测量泪液分泌体积、角膜荧光素钠染色评价角膜损伤;治疗第14天麻醉状态下处死大鼠采集角膜标本,使用HE染色观察角膜形态学改变,PAS染色计数结膜杯状细胞。结果:泪液体积结果显示,治疗前,各治疗组大鼠与生理盐水组之间泪液体积的差异均无统计学意义(P>0.05),治疗第7天时,4E组和混合组大鼠泪液体积大于生理盐水组和4Z组大鼠(P<0.01或P<0.05),治疗第14天各治疗组大鼠的泪液体积明显大于生理盐水组大鼠(P<0.01);角膜荧光素纳染色评分结果显示,治疗前各治疗组大鼠与生理盐水组染色评分比较差异均无统计学意义(P>0.05),治疗第7天时4E组大鼠评分低于与生理盐水组(P<0.05),治疗第14天各治疗组大鼠评分明显低于生理盐水组(P<0.01);HE染色结果显示,与生理盐水组大鼠相比,各治疗组大鼠角膜的病理变化减轻;PAS染色结果显示,各治疗组大鼠结膜杯状细胞数量高于生理盐水组大鼠(P<0.05或P<0.01),4E组和混合组则分别均高于4Z组(P<0.05)。结论:4Z、4E及混合式吉法酯对干眼症大鼠的角膜有保护作用,4E构型吉法酯的效果更好,其保护机制可能与吉法酯增加泪液分泌和减少角膜杯状细胞数有关。
Objective: To investigate the protective effect of different configurations of gemcitabine on scopolamine hydrobromide-induced dry eyes in rats. Methods: Wistar female rats were randomly divided into the normal group, 1% gemcitabine treatment group(4 Z gefarnate, 4 e gefarnate, 4 Z+4 E gefarnate) and the saline control group(n=8). The normal group was not treated at all. In the other groups, the rat dry eye model was established by subcutaneous injection of scopolamine hydrobromide combined with a fan to simulate the environment of high circulation and low humidity. The basis of the Shirmer I test was evaluated on the 7~(th) and 14~(th) days after treatment. The corneal damage volume was evaluated by tear secretion volume and corneal fluorescein staining. The corneal morphological changes were evaluated by HE staining on the 14~(th) day after treatment, and the effect of PAS staining on the number of conjunctival goblet cells was evaluated. Results: On the 7~(th) day of treatment, compared with the saline control group, the 4 E configuration ofgefarnate significantly increased the tear volume(P<0.01) and decreased the corneal fluorescein sodium staining scores(P<0.05) in dry eye rats; All configurations of gefarnate significantly increased tear volume(P<0.05) and decreased corneal fluorescein sodium staining scores(P<0.05). HE staining showed that the corneal upper cells in different treatment groups had different degrees of pathological changes, and compared with the 4 Z configuration, the 4 E configuration ofgefarnate had better effect on corneal morphology than the 4 Z configuration. The results of PAS staining showed that the genomic esters of all configurations significantly increased the number of conjunctival goblet cells in dry eye rats, and the number of goblet cells in the 4 E configuration group was significantly higher than that in the 4 Z configuration group(P<0.05). Conclusion: Both 4 Z and 4 E configurations have protective effect on cornea of rats with dry eyes, and 4 E configuration is superior to 4 Z configuration in tear volume recovery and corneal injury repair.

关键词(KeyWords)： 大鼠,Wistar;吉法酯;角膜;干眼症;构型;结膜杯状细胞
rats,Wistar;gefarnate;cornea;dry eye;configurations;conjunctival goblet cells

Abstract:

Keywords:

基金项目(Foundation): 贵州省科学技术基金项目[黔科合JZ字(2015)2001];; 贵州省科技计划项目[黔科合(2016)支撑2848];; 贵州省教育厅青年科技人才成长项目[黔教合KY字(2017)155]

作者(Author): 糜玲,周波,李永,彭金刚,汤磊,黄家宇
MI Ling,ZHOU Bo,LI Yong,PENG Jingang,TANG Lei,HUANG Jiayu

DOI: 10.19367/j.cnki.1000-2707.2020.01.009

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