The Effect And Mechanism Of MicroRNA-144 Inhibitor On Reflux Esophagitis

Objective: To investigate the effect and mechanism of micro RNA-144 inhibitor(mi R-144 antagomir)in reflux esophagitis(RE).Methods: A total of 48 male Sprague Dawley rats were divided into three groups randomly,including sham operation control group(control group,n=16),reflux esophagitis group(RE group,n=16)and mi R-144 antagomir-treat group(treat group,n=16).RE rat models were established by ligating fore-stomach and constricting proximal duodenum.After surgery,all rats were kept in separate cages and starved of food for 24 hours but had free access to water.1ml of normal saline was injected into the tail vein of each rat in control group and RE group once a day,and 5OD(1ml)of mi R-144 antagomir was injected into the tail vein of each rat in treat group once a day for 3 days after surgery.Rats were sacrificed 14 days after surgery,and the esophagus of each rat was taken for general observation,histological examination and immunohistochemical detection.The expression of Nrf2,CD68,i NOS,MMP3 and MMP9 in esophageal mucosa were detected by immunohistochemical staining to analyse the degree of inflammation,oxidative stress and mucosal barrier dysfunction.Results: The appetite and activity of rats in RE group and treat group decreased after surgery,and improved gradually about 4 days later.All of rats in control group recovered well.The average weight of rats in RE group and treat group were lower than that in control group after surgery(P<0.05).The survival rates of RE group and treat group were both 87.50%.RE appeared in RE group and treat group.The rate of sever esophagitis of treat group was lower than that of RE group(14.29% vs 50.00%,P<0.05).The expression of Nrf2,CD68,i NOS,MMP3 and MMP9 in RE group and treat group were significantly higher than those in control group(P<0.05).Compared with the RE group,the expression of Nrf2 in esophageal mucosa was significantly increased(0.37±0.02 vs 0.29±0.03,P<0.05),and the expressions of CD68,i NOS,MMP3 and MMP9 were significantly decreased(P<0.05)in treat group.The expression of CD68 was positively correlated with the expressions of MMP3(r=0.985,P<0.05)and MMP9(r=0.975,P<0.05).The expression of i NOS was positively correlated with the expressions of MMP3(r=0.906,P<0.05)and MMP9(r=0.900,P<0.05).Conclusion: Mi R-144 inhibitor have protective effect on RE,which is related with Nrf2 activation,so as to alleviate the inflammation and oxidative stress of esophageal mucosa and protect esophageal mucosa barrier.