环孢素A滴眼液治疗结膜干燥综合征的机理探讨

The research about the mechanism of Cyclosporina A gutta treating keratoconjunctivitis sicca

目的 建立结膜干燥综合征的动物模型。证实实验动物出现结膜干燥综合征后，予以环孢素A(CsA)滴眼液治疗，观察环孢素A滴眼液对结膜干燥综合征的治疗效果，治疗前后结膜杯状细胞的数量、结膜上皮细胞和杯状细胞及腺样层水通道蛋白3(AQP3)表达量的变化以及淋巴细胞浸润程度的改变。方法 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塾、背部皮下及四肢腋下淋巴结，诱导结膜干燥综合征动物模型，再用环孢素A滴眼液予以治疗。观察对照组与实验组、实验组治疗前后泪液分泌量、泪膜破裂时间的变化；作病理切片观察结膜杯状细胞破坏程度及破坏后的恢复程度，淋巴细胞浸润程度；用免疫组化SP法测量结膜上皮细胞和杯状细胞及腺样层AQP3表达量的变化。结果 CsA滴眼液治疗前后小鼠泪液分泌量、泪膜破裂时间、结膜杯状细胞数和AQP3表达量都有明显变化，淋巴细胞浸润程度减轻。结论 CsA滴眼液对结膜干燥综合征有明显的治疗作用，治疗的机理包括抑制淋巴细胞，增加结膜杯状细胞的数量，上调结膜上皮细胞和杯状细胞及腺样层AQP3的表达量。

Objective To observe the therapeutic efficacy of cyclosporinA（CsA） gutta to keratoconjunctivitis sicca and the expression of aquaporin - 3 （ AQP3 ） in conjunctiva before and after the therapy. We erected animal model of keratoconjunctivitis sicca first. Method To induce the animal model of keratoconjunctivitis sicca, we used Pertussis vaccine ＋ CFA ＋ antigen of the same typle mouse＇s conjunctiva; Then we treated keratoconjunctivitis sicca with CsA gutta, and observed breaking up time（ BUT）, amount of lacrimal secretion before and after the therapy; Utilized pathological ection, we could observe the reablement of the conjunctiva beaker cell and the change of AQP3 with immunohistochemical method. Results The amount of lacrimal secretion, BUT and the expression of AQP3 had markedly change. The cell that had depauperatod had some recovery. Conclusion Csa gutta has marked therapeutical effect on keratoconjunctivitis sicca by inhibiting T lymphcell, increasing the amount of goblet cell and AQP3 in conjunctiva.