Effects of polydatin on inflammatory response in dry eye disease rats and its mechanism
OBJECTIVE To investigate the effects of polydatin(PD)on the inflammatory response in dry eye disease(DED)rats and its potential mechanism based on protein kinase A(PKA)/cyclic adenosine monophosphate response element binding protein(CREB)signaling pathway.METHODS Male SD rats were randomly divided into blank control group(normal group),model group(simple DED group),0.05％PD group,0.5％PD group and 0.5％PD+PKA inhibitor H-89 group(0.5％PD+H-89 group),with 15 rats in each group.Except for the normal group,the rats in other groups were prepared with a DED model by injecting scopolamine hydrobromide 12.5 mg/d onto the surface of eyeball.At the same time,each drug group was given corresponding liquid medicine(0.5％or 0.05％PD,eye drip,3 times a day;1 mg/kg H-89,intraperitoneal injection,once a day)for 7 d in total.The tear secretion,corneal fluorescein staining score and conjunctival goblet cell density of rats were detected in each group;the pathological changes of corneal tissues were observed,and the levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6)and the expression of PKA/CREB signaling pathway-related proteins were detected in corneal tissues.RESULTS Compared with normal group,the corneal epithelium of rats in the simple DED group was thickened,stromal layer cells were disordered and partially absent,nuclear spacing was larger,and a large number of inflammatory cells infiltrated;the tear secretion,conjunctival goblet cell density and the phosphorylation levels of PKA and CREB in corneal tissues were reduced significantly,while the corneal fluorescein staining score and the levels of inflammatory factors in corneal tissue were increased significantly(P＜0.05).Compared with the simple DED group,the pathological injuries of corneal tissues of rats in 0.05％PD and 0.5％PD groups were alleviated,each quantitative index was significantly improved,and the improvement effect of 0.5％PD group was more obvious(P＜0.05).H-89 could reverse the improvement effect of PD on each index significantly(P＜0.05).CONCLUSIONS PD can increase tear secretion and the conjunctival goblet cell density,and reduce the inflammatory response and pathological injury of corneal tissue in DED rats.The above effects are related to the activation of PKA/CREB signaling pathway.
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