The Research Of Minocycline Regulate Inflammation In Corneal Alkali Burn Through Mapk Signaling Pathway

Purpose: 1)To study the effect of minocycline on inflammatory reaction of corneal alkali burns in rats;2)To elucidate whether minocycline modulates the inflammation of corneal alkali burns in rats through MAPK signaling pathway.Methods: A total of 120 SPF Sprague Dawley rats were randomly assigned 24 as blank control group,The others were selected right eye to establish with grade III corneal alkali burn model by immersing circular filter paper with 1 mol / l Na OH,left eye without any treatment.After modeling,they were randomly divided into corneal alkali burn group,minocycline group,anisomycin group,minocycline + anisomycin group(combined treatment group).At each time point,six rats(6 eyes)were randomly selected from each group to observe the corneal condition of the rats,take a picture of the anterior segment and evaluate the corneal inflammation index.The rat's eyeballs were removed immediately after the neck was ablated,and the immunohistochemistry was made for the pathological tissue section.The corneal histopathological changes were observed.The relative optical density index of IL-1?,TNF-?,P38 MAPK and ERK1 / 2 were calculated.At the same time,the m RNA relative expression of P38 MAPK and ERK1 / 2 in rat corneal was detected by reverse transcription-polymerase chain reaction(RT-PCR),and the differences between groups were analyzed to evaluate the curative effect of minocycline on corneal alkali burn in rats Correlation with MAPK signaling pathways.Results: 1)The inflammation index significantly increased after corneal alkali burn,reaching the peak on the 7th day,and then gradually decreased,with statistical significance on the 1st day,the 4th day,the 7th and the 14 th days(P<0.05).2)The expression of IL-1?,TNF-?,P38 MAPK,ERK1/2 in normal corneal tissue was low or not expressed.The expression of IL-1?,TNF-?,P38 MAPK and ERK1/2 increased after corneal alkali burn and peaked on the 7th day,and then decreased gradually.with statistical significance on the 1st day,the 4th day,the 7th and the 14 th days(P<0.05).3)Compared with corneal alkali burn group,Immunohistochemistry indicated that the expression of IL-1?,TNF-?,P38 MAPK and ERK1/2 in minocycline group was decreased,with statistical significance on the 7th day(P<0.05).The expressions of IL-1?,TNF-?,P38 MAPK and ERK1/2 in anisomycin group were significantly increased,with statistical significance on the 4th day,the 7th and the 14 th days(P<0.05).The expression of IL-1?,TNF-?,P38 MAPK and ERK1/2 in the combined treatment group was decreased,with statistical significance on the 7th day(P<0.05).Compared with the minocycline group,the expression of IL-1?,TNF-?,P38 MAPK and ERK1/2 in anisomycin group were significantly increased,with statistical significance on the 4th day,the 7th and the 14 th days(P<0.05).the expression of IL-1?,TNF-?,P38 MAPK and ERK1/2 in the combined treatment group were slightly increased,the expression of ERK1/2,IL-1 beta,IL-1?,TNF-? with No significant difference on the 1st day,the 4th day,the 7th and the 14 th days(P>0.05).P38 MAPK with statistical significance on the 4th day(P<0.05),ERK1/2 with statistical significance on the 7th day(P<0.05).4)Compared with the corneal alkali burn group,RT-PCR indicated that the m RNA expression of P38 MAPK and ERK1/2 in the minocycline group was the highest on the 1st day,and then decreased gradually,with statistical significance on the 4th day,the 7th and the 14 th days(P<0.05).The m RNA expression of P38 MAPK and ERK1/2 were significantly increased in the anisomycin group,reached the peak on the 7th day,with statistical significance on the 1st day,the 4th day,the 7th and the 14 th days(P< 0.05).the m RNA expression of P38 MAPK and ERK1/2 were slightly increased in the combined treatment,reached the peak on the 7th day,P38 MAPK with statistical significance on the 1st day(P< 0.05),ERK1/2 with statistical significance on the 1st day,the 4th day(P< 0.05),Compared with the minocycline group,the m RNA expression of P38 MAPK and ERK1/2 in the anisomycin group and the combined treatment group was increased,with statistical significance on the 4th day,the 7th and the 14 th days(P< 0.05)Conclusion: 1)Minocycline can inhibit the inflammatory of corneal alkali burn;2)The MAPK signaling pathway may be involved in the inflammatory response process of corneal alkali burn,and minocycline may regulate the MAPK signaling pathway by inhibiting P38 MAPK and ERK1/2 to inhibit the inflammatory response of corneal alkali burn.