东莨菪碱与苯扎氯铵干眼症大鼠造模方法研究

Study on Dry Eye Modeling by Scopolamine and Benzalkonium Chloride in Rats

为比较氢溴酸东莨菪碱皮下注射与苯扎氯铵滴眼制作干眼症动物模型的各自特点,将健康SD大鼠随机分为正常组、东莨菪碱加风组、苯扎氯铵组和吹风对照组。正常组不接受任何处理;东莨菪碱组皮下注射氢溴酸东莨菪碱注射剂;苯扎氯铵组以2mg/mL苯扎氯铵滴眼液每日3次滴眼;吹风组仅置于吹风装置中每日12h。于试验第3、7、10天检查Schirmer I试验(SIT)、泪膜破裂时间(BUT)、角膜荧光素染色(FLS)。结果表明,东莨菪碱组在第3、7、10天,SIT与正常组相比具有显著差异(P<0.05),第7、10天BUT和FLS与正常组相比具有显著差异(P<0.05);苯扎氯铵组在试验第7、10天,SIT试验和BUT与正常组相比有显著差异(P<0.05),BUT第10天差异达到最大,在第3、7、10天,FLS与正常组相比具有显著差异(P<0.05);组织病理学检查东莨菪碱组泪腺较苯扎氯铵组明显有腺上皮细胞萎缩;苯扎氯铵组大鼠角结膜上皮细胞明显变薄,表层细胞排列紊乱,细胞数量显著减少,并存在炎性细胞浸润。提示造模10d氢溴酸东莨菪碱注射剂皮下注射配合吹风制作的干眼症动物模型对大鼠泪腺及眼表上皮细胞影响显著,伴有较轻程度的眼表损伤,更适合早期轻中度干眼造模;苯扎氯铵滴眼造模方法易造成眼表上皮损伤,适合短期重度干眼的造模。

To compare the dry eye models developed by subcutaneous injection of scopolamine hydrobromide and eye drops of benzalkonium chloride in rats respectively,healthy SD rats were randomly divided into 4 groups, normal group（NG）, scopolamine plus blowing group（SG）, benzalkonium group （BZG） and blowing group （BG） ,5 rats in each group. The rats in the NG didn＇t receive any treatment,while rats in SG were ad- ministered alternatively into the lower limbs with 0.5 mL scopolamine hydrobromide （0.6 mg/0.1 mL） （ 4 times a day ）,the rats in the BZG were given with eye drops of benzalkonium chloride （ 2 mg/mL ） three times a day,and the rats in the BG were kept in the blowing device for 12 h everyday. Then,Schirmer I test （S I T）, tear membrane breakup time （BUT） and fluorescein staining （FLS） were tested in each group. After experiment, the inter-group comparison of SIT in SG and NG showed statistically signifi- cance on day 3,7 and 10 （P〈0. 05） ,and the comparison of BUT and FLS showed statistically significance on day 7 and 10 （P〈0.05）. For rats in BZG,the inter-group comparison of SIT and BUT with NG showed statistically significance on day 7 and 10 （P〈0. 05） ,the most substantial changes of BUT appeared at day 10, and the comparison of FLS with NG showed statistical significance （P〈0.05）. Histopathological exam- ination of lacrimal gland showed a more obvious atrophy of glandular epithelial cells in SG when compared with that in BZG;Rats in BZG showed a thinner corneal surface, chaotic cell arrangement, a reduction of the cell number and infiltration of inflammatory cells which indicated that at day 10,the subcutaneous injection of scopolamine hydrobromide combined with blowing method had obvious influence on lacrimal gland and ocular epithelium cells in rats with an ocular surface damage in a mild degree which is suitable for creating mild to moderate dry eye model in early stage,while eye drops of benzalkonium method can cause damage to ocular surface more easily which is more suitable for creating severe dry eye in a short period.