雌激素对小鼠结膜干燥综合征的实验观察

Therapeutic action and mechanism of estrogen on treating keratoconjunctivitis sicca

目的:探讨雌激素对小鼠结膜干燥综合征的治疗作用及机制。方法:应用百日咳疫苗+完全弗氏佐剂+同种鼠结膜抗原,多点注射于小鼠的足墊、背部皮下及四肢腋下淋巴结,诱导产生结膜干燥综合征小鼠模型;用不同剂量的雌激素予以治疗。观察各组的泪液分泌量、泪膜破裂时间;作病理切片观察结膜杯状细胞变化和淋巴细胞浸润程度;用免疫组化SP法测量结膜上皮细胞、杯状细胞及腺样层AQP3表达量的变化。结果:较大剂量的雌激素(200mg.kg-1.d-1)治疗前后小鼠泪液分泌量增加,泪膜破裂时间延长,结膜内淋巴细胞浸润程度减轻,AQP3表达量和结膜杯状细胞数增加(P<0.05);普通剂量的雌激素治疗组(20mg.kg-1.d-1)无明显变化。结论:较大剂量的雌激素对结膜干燥综合征有明显的治疗作用,治疗的机制包括增加结膜杯状细胞的数量,上调结膜上皮细胞、杯状细胞及腺样层AQP3的表达量,抑制淋巴细胞;但普通剂量的雌激素无明显治疗作用。

OKIECTIVE The mechanism of estrogen on treating Keratoconjunctivitis Sicca（KCS） was studied. METHODS The KCS Model were established by injecting Pertussis Vaccine ＋ CFA ＋ antigen of the same typle mouse＇s conjunctiva, Then the KCS Models were treated with estrogen（E2）. Changes in breaking up time（BUT）, amounts of lacrimal secretion in 30 min and diversion in 24 h were measured, The percentage of beaker cells, the degree of lymphocytic infiltration in conjunctiva were observed by using pathological section. The expression levels of Aquaporin-3（AQP3） in eonjunctiva epithelial cell, beaker cell and accessory lacrimal gland were detected by using immunohistochemical method in different group. RESULTS In the groups treated with E2 at dose of 200 mg.kg^-1 .d^-1, the amount of lacrimal secretion（in 30 min）, breaking up time and the expression of AQP3 had markedly changed in contrast to the group before the therapy, the beaker cell that had depauperated had some recovery in animals and the degree of lymphocytic infiltration in conjunctiva had decreased. There had no marked change in animals treated with E2 at dose of 20 mg·kg^-1·d^-1. CONCLUSION E2 at dose of 200 mg·kg^-1·d^-1 has marked therapeutical effect on KCS by inhibiting T lympheell, increasing the amount of goblet cell and AQP3 in conjunctiva.