目的：观察不同浓度的密蒙花滴眼液对去势雄兔干眼结膜炎性因子IL-1β、黏蛋白5AC(MUC5AC)及P38MAPK表达的影响，从而探讨密蒙花滴眼液对干眼的疗效。

方法：将36只雄兔随机分为：空白组、模型组、密蒙花滴眼液低浓度组(1mg/mL)、中浓度组(1.5mg/mL)、高浓度组(3mg/mL)、睾酮组。除空白组外各组均行睾丸及附睾切除建立干眼动物模型，造模成功后，空白组和模型组不予以处理，密蒙花滴眼液低浓度组(1mg/mL)、中浓度组(1.5mg/mL)、高浓度组(3mg/mL)给予密蒙花不同浓度滴眼液，3次/d，睾酮组按0.5mL/kg剂量在大腿肌肉处注射丙酸睾酮，每3d 1次，各组分别于造模前和用药4wk后在全身麻醉下检测荧光素染色、SchirmerⅠ试验(SⅠt)和泪膜破裂时间(BUT)。用药4wk后处死兔子，取其双眼球结膜组织，采用免疫组织化学染色法检测结膜中IL-1β、MUC5AC、P38MAPK的表达。

结果：密蒙花滴眼液低浓度组、中浓度组、高浓度组用药4wk后，SⅠt值明显高于模型组，BUT值明显长于模型组，角膜荧光素染色阳性较模型组有明显改善(均P<0.01)。密蒙花滴眼液低浓度组、中浓度组、高浓度组结膜IL-1β、P38MAPK的阳性表达低于模型组，MUC5AC的表达高于模型组(P<0.01)，密蒙花滴眼液高浓度组优于低浓度、中浓度组。

结论：密蒙花滴眼液具有类雄激素效果，对于去势雄兔干眼可以下调干眼结膜组织中IL-1β、P38MAPK的表达，增加MUC5AC的表达，从而减少干眼结膜组织的炎症浸润，维持泪膜稳定性，但其作用弱于雄激素。密蒙花滴眼液中、高浓度组对于干眼治疗作用强于低浓度组，高浓度组优于中浓度组。

AIM: To observe the effects of butterflybush flower eye drops at different concentrations on expression of inflammatory crtokines IL-1β, Mucin 5AC(MUC5AC)and P38MAPK in castrated male rabbits, and to explore the therapeutic effect of that drops on dry eyes.

METHODS: Thirty-six male rabbits were randomly divided into blank group(A), model group(B), low concentrations butterflybush flower eye drops group(C, 1mg/mL), the medium concentrations drops group(D, 1.5mg/mL), the high concentrations drops group(E, 3mg/mL), and testosterone group(F). In addition to group A, the testes and epididymis were removed from each group to establish a dry eye animal model. After successful modeling, groups A and B remain unchanged. Groups C, D, and E were given different concentrations of butterflybush flower eye drops, 3 times/d. In group F, testosterone propionate was injected into the muscles of the thigh at a dose of 0.5mL/kg once every 3d. Fluorescein staining, Schirmer I test(SⅠt)and tear film break time(BUT)were measured under general anesthesia in each group, eatment. After 4wk of treatment, the rabbits were sacrificed and the conjunctival tissues of the eyes were taken. The expression of IL-1β, mucin 5AC and P38MAPK in the conjunctiva was detected by immunohistochemical staining.

RESULTS: Among low concentrations butterflybush flower eye drops group, the medium concentrations drops group and the high concentrations drops group, the SⅠt value was significantly higher than that of model group, and BUT was significantly longer than model group. The positive staining of corneal fluorescein was significantly improved compared with model group, which was statistically significant(P<0.01). Among IL-1β and P38MAPK in the conjunctiva of high concentrations butterflybush flower eye drops group, the medium concentrations drops group and the low concentrations drops group, the positive expressions were lower than those in model group, and the expression of MUC5AC was higher than that in group model group(P<0.01). In addition, the high concentrations drops group was superior to the low and the medium concentrations drops group.

CONCLUSION: Butterflybush flower eye drops have androgen-like effect. For castrated dry eyes of male rabbits, they can down-regulate the expression of IL-1beta and P38MAPK in dry conjunctival tissue and increase the expression of MUC5AC, thus reducing inflammation infiltration in dry conjunctival tissue and maintaining tear film stability, but their effect is weaker than that of androgen. To the treatment of dry eyes, the middle and high concentration groups of the drops had stronger effects than the low one, and the high concentration group was better than the medium one.

国家自然科学基金面上资助项目(No.30772824,81574031); 湖南省高层次卫生人才“225”工程培养项目资助[No.湘卫人发(2013)13号]; 等