目的探讨兔皮下注射氢溴酸东莨菪碱建立干眼模型的有效性和眼表病理损害机制。设计实验研究研究对象健康新西兰大白兔9只。方法将9只白兔随机分为三组,每组3只。实验组皮下注射氢溴酸东莨菪碱,其中低剂量组(L,1.0 mg/次)、高剂量组(H,2.0 mg/次),对照组注射等量生理盐水。注射时间点为每天8点、11点、14点和18点,连续30天。主要指标不同时间点用药前后泪液分泌量、泪膜破裂时间,角膜荧光素染色情况,结膜印迹联合PAS染色评价眼表上皮细胞表型。观察期末取角结膜、泪腺组织行HE染色光镜下观察。结果酚红棉线法测得高剂量(H)组注射前泪液分泌量为(16.25±2.299)mm,第21d时下降为(6.75±1.982)mm,对照组为(16.50±2.619)mm,差异具有统计学意义(P=0.000<0.01),同期低剂量组(L)为(15.00±2.390)mm,与对照组相比无明显差异。H组第3d出现BUT缩短,L组则第7d发生BUT的变化,此后BUT值均低于5s,对照组BUT大于20s。实验组均出现角膜荧光素染色阳性,H组出现时间早(3 d),持续时间长。L组和H组PAS染色与对照组相比,杯状细胞形态紊乱、核淡染,部分核固缩,L组和H组之间无明显差异。HE染色显示H组泪腺周围见散在淋巴细胞和腺腔凋亡性改变,角膜上皮呈重度瘤样增生基质层变性伴水肿,结膜杯状细胞反应性增多,固有层见淋巴细胞浸润数量增加。L组角膜浅层上皮轻度增生,细胞排列稍紊乱,结膜和泪腺组织病理改变轻微。结论兔皮下注射氢溴酸东莨菪碱,4次/d,2.0 mg/次,可有效维持药物外周浓度,抑制泪腺分泌,引起角结膜上皮损伤,成功建立以泪液缺乏为主,炎症反应参与的干眼动物模型,为进行干眼发病机制研究和药物干预提供了理想的实验平台。 Objective To investigate the effectiveness of subcutaneously injected scopolamine hydrobromide into establishing a dry eye model and the ocular pathological damage mechanism. DESIGN EXPERIMENTAL RESEARCH The study was conducted on 9 healthy New Zealand white rabbits. Methods Nine white rabbits were randomly divided into three groups of three. In the experimental group, scopolamine hydrobromide was injected subcutaneously. The rats in the low dose group (1.0 mg / L, L, 2.0 mg / dose) and the control group received the same amount of normal saline. The injection time point is 8 o’clock, 11 o’clock, 14 o’clock and 18 o’clock every day for 30 consecutive days. The main indexes at different time points before and after administration of tear fluid volume, tear film rupture time, corneal fluorescein staining, conjunctival blot combined with PAS staining eyelid epithelial cell phenotype. Observed at the end of the conjunctiva, lacrimal gland tissue under HE staining under light microscopy. Results The amount of tear fluid in high dose (H) group before injection was (16.25 ± 2.299) mm, decreased to (6.75 ± 1.982) mm on the 21th day and (16.50 ± 2.619) mm on the control, Statistical significance (P = 0.000 <0.01), low dose group (L) was (15.00 ± 2.390) mm, no significant difference compared with the control group. BUT was shortened in the third day of H group, BUT was changed in the seventh day in the L group, BUT value was lower than 5 seconds, BUT in the control group was more than 20 seconds. Corneal fluorescein staining was positive in the experimental group, the early appearance of H group (3 d), long duration. Compared with the control group, PAS staining in L group and H group showed that the morphology of goblet cells was disordered, nuclear light staining, partial nuclear pyknosis, and there was no significant difference between L group and H group. Hematoxylin and eosin staining showed that the apoptotic changes of scattered lymphocytes and glandular cavity around the lacrimal gland were observed in group H. The corneal epithelium showed degeneration and degeneration of stromal cells with severe tumor-like hyperplasia. The reactivity of conjunctival goblet cells increased and the number of lymphocytes infiltration in lamina propria increased. L group mild epithelial epithelial mild hyperplasia, cell arrangement slightly disorder, pathological changes in the conjunctiva and lacrimal gland minor. Conclusion Scopolamine hydrobromide injected subcutaneously once a day for 4 times / d and 2.0 mg / time can effectively maintain the peripheral concentration of drug and inhibit the secretion of lacrimal gland, resulting in the damage of corneal conjunctiva epithelium. The dry eye with lacrimal fluid deficiency and inflammatory reaction is successfully established Animal models provide an ideal experimental platform for the study of dry eye pathogenesis and drug intervention.