Objective To investigate the therapeutic effect and mechanism of MCC950 on benzalkonium chloride-in-duced dry eye(DED)in rats.Methods Among 60 male SD rats,50 rats were treated with 20 g·L-1 benzalkonium chlo-ride solution 3 times a day in both eyes to induce DED model,and a significant decrease in tear secretion was regarded as a successful modeling,and the remaining 10 rats were regarded as the control group.DED rats were randomly divided into 5 groups:DED,DED+10MCC950,DED+50MCC950,DED+100MCC950,and DED+500MCC950 groups,and were given 0.2 mL of 0,10,50,100,and 500 μmol·L-1 MCC950 in both eyes for two weeks,and then examined the amount of tear secretion,corneal histopathology(HE staining),reactive oxygen species(ROS),and inflammation factors(NLRP3,Caspase-1,IL-1β,IL-6).Results The tear secretion of rats in the DED group was significantly lower than that of the control group(P＜0.05).Except for the DED+10MCC950 group,the tear secretion of rats in different concentrations of MCC950 treatment groups was increased and positively correlated with the MCC950 dose(all P＜0.05).HE staining of the cornea showed that compared with the control group,the cornea of the DED group was significantly thinner,the arrange-ment of surface cells was disorganized,the number of cells was significantly reduced,and a large number of"vacuole"-like structures appeared;the corneal stroma was disorganized and sparsely structured.The degree of histopathological changes in the cornea of rats treated with different concentrations of MCC950 decreased with the increase of the concentration of MCC950.Compared with the control group,the relative expression level of ROS in the DED group of rats was significantly increased(P＜0.05).In each MCC950 treatment group,as the concentration of MCC950 increased,the relative expression level of corneal ROS staining in rats gradually decreased,showing a concentration-dependent effect(all P＜0.05).Com-pared with the control group,the levels of NLRP3,IL-1 β,Caspase-1 and IL-6 were significantly increased in the DED group(all P＜0.05).The levels of various inflammatory factors were dose-dependently reduced in the MCC950 treatment groups(all P＜0.05).Conclusion MCC950 can reduce oxidative stress and inflammation and improve the symptoms of benza-lkonium chloride-induced DED in rats by inhibiting the activation of NLRP3 inflammatory vesicles.

Objective To investigate the therapeutic effect and mechanism of MCC950 on benzalkonium chloride-in-duced dry eye(DED)in rats.Methods Among 60 male SD rats,50 rats were treated with 20 g·L-1 benzalkonium chlo-ride solution 3 times a day in both eyes to induce DED model,and a significant decrease in tear secretion was regarded as a successful modeling,and the remaining 10 rats were regarded as the control group.DED rats were randomly divided into 5 groups:DED,DED+10MCC950,DED+50MCC950,DED+100MCC950,and DED+500MCC950 groups,and were given 0.2 mL of 0,10,50,100,and 500 μmol·L-1 MCC950 in both eyes for two weeks,and then examined the amount of tear secretion,corneal histopathology(HE staining),reactive oxygen species(ROS),and inflammation factors(NLRP3,Caspase-1,IL-1β,IL-6).Results The tear secretion of rats in the DED group was significantly lower than that of the control group(P＜0.05).Except for the DED+10MCC950 group,the tear secretion of rats in different concentrations of MCC950 treatment groups was increased and positively correlated with the MCC950 dose(all P＜0.05).HE staining of the cornea showed that compared with the control group,the cornea of the DED group was significantly thinner,the arrange-ment of surface cells was disorganized,the number of cells was significantly reduced,and a large number of"vacuole"-like structures appeared;the corneal stroma was disorganized and sparsely structured.The degree of histopathological changes in the cornea of rats treated with different concentrations of MCC950 decreased with the increase of the concentration of MCC950.Compared with the control group,the relative expression level of ROS in the DED group of rats was significantly increased(P＜0.05).In each MCC950 treatment group,as the concentration of MCC950 increased,the relative expression level of corneal ROS staining in rats gradually decreased,showing a concentration-dependent effect(all P＜0.05).Com-pared with the control group,the levels of NLRP3,IL-1 β,Caspase-1 and IL-6 were significantly increased in the DED group(all P＜0.05).The levels of various inflammatory factors were dose-dependently reduced in the MCC950 treatment groups(all P＜0.05).Conclusion MCC950 can reduce oxidative stress and inflammation and improve the symptoms of benza-lkonium chloride-induced DED in rats by inhibiting the activation of NLRP3 inflammatory vesicles.