Polydatin activates MEK/ERK signaling pathway to improve ocular surface dysfunction and pathology in rats with scopolamine-induced dry eye disease
Objective:To explore effect of polydatin on ocular surface dysfunction and pathology in dry eye disease(DED)rats and its protective mechanism.Methods:Eighteen from 90 SD rats were randomly chosen as control group,and other rats were injected subcutaneously with scopolamine hydrobromide to establish DED model.After modeling,rats were separated into model group,0.05%polydatin group,0.5%polydatin group,0.5%polydatin+U0126[mitogen-activated protein kinase kinase(MEK)inhibi-tor]group,with 18 rats in each group;each administration group was given corresponding doses of drugs for intervention,and rats in control group and model group were given same amount of normal saline.On the 7th,14th,21st,and 28th day of intervention,Schirmer test was performed to measure tear secretion amount of rats in each group,fluorescein staining was performed to measure tear film breakup time(BUT)and corneal damage of rats in each group;RT-qPCR was performed to measure mRNA expression of pro-inflammatory factors TNF-α,IFN-γ and IL-1β in cornea and conjunctival tissues;HE staining was performed to observe histopatho-logical changes of cornea;PAS staining was performed to evaluate number of conjunctival goblet cells;Western blot was performed to detect expressions of MEK/extracellular regulatory protein kinase(ERK)pathway related proteins.Results:Compared with control group,tear secretion amount BUT and number of conjunctival goblet cells in model group were obviously reduced(P<0.05),corneal injury score,TNF-α,IFN-γ and IL-1β mRNA levels were obviously increased(P<0.05),corneal epithelial layer was thinned,a large number of inflammatory cell infiltration and new capillaries could be seen;compared with model group,tear secretion amount,BUT,number of conjunctival goblet cells,p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 in 0.05%polydatin group and 0.5%polydatin group were obviously increased(P<0.05),corneal injury score,TNF-α,IFN-γ and IL-1β mRNA levels were obviously reduced(P<0.05),pathological damage of corneal tissue was obviously relieved;U0126 could significantly attenuate protective effects of polydatin on ocular surface dysfunction and pathological changes in DED rats.Conclusion:Polydatin may improve ocular surface dysfunction and pathology of DED rats induced by scopolamine by activating MEK/ERK pathway.
Dry eye diseasePolydatinInflammationOcular surface dysfunctionMitogen-activated protein kinase kinaseExtracellular regulated protein kinase
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维普
