METHODS:Thirty healthy 8-week-old male Brown Norway rats were randomly assigned into three groups equally. The left eye of group A was blank group, group B was the left lacrimal gland extirpation model, the left tear gland of group C was injected with botulinum toxin A. We compared the data of Schirmer I test, tear break-up time(BUT), and the corneal fluoresceince staining scores at different times(1d before experiment, 3d, 7d, 14d, 28d, and 42d after the surgical process). We observed pathological changes of conjunctiva, cornea and lacrimal gland at 42d, and we used real-time polymerase chain reaction to analyze interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and epithelial growth factor(EGF).

RESULTS:At the 3d, compared with group A, the tear secretion of both group B and group C were continuous decrease(P<0.05). At the 7d, compared with group A, the BUT of both group B and group C began to decreased(P<0.05), and the corneal epithelial staining scores of both group B and group C began to significantly increase(P<0.05). There was no statistical difference in the above clinical data between group B and group C(P>0.05). The corneal epithelial cells in group A was set as normal morphology, while the corneal epithelial cells in group B and group C showed filamentous separation of surface cells to varying degrees, and the number of conjunctival goblet cells was decreased. The lacrimal gland of group C was obviously atrophic. In conjunctival and corneal tissues, the expression of EGF, TNF-α and IL-6 were significantly increased in group B and group C, which was statistically significant compared with group A(P<0.05). The expression of EGF and TNF-α didn't altered significantly between group B and group C(P>0.05), however, the expression of IL-6 in group B was much higher than that in group C(P<0.05).

CONCLUSION:In this study, we proved that both lacrimal gland extirpation and lacrimal gland injection botulinum toxin A could construct a stable aqueous tear deficiency dry eye rat model. The appropriate animal model should be selected according to the experimental design and research purpose.