The Role Of Resolvin D1 On Acute Reflux Esophagitis With DHA Intervention In Rats

Objective: To investigate the role of Resolvin D1(RvD1) on acute reflux esophagitis(RE) in rats with DHA intervention and the potential mechanisms.Methods: Male SD rats of clean grade were randomly divided into 4 groups,including DMSO group, RvD1 group, BOC-2(inhibitor of RvD1 receptor) group and DHA+BOC-2 group(n=10, respectively). Rat RE model was established by pyloric clip and section ligation. Intervention drugs, including 0.25ml/kg DMSO solvent, 0.25mg/kg DHA solution, and 0.5mg/kg BOC-2 solution were intraperitoneal injected to the rats at2 h prior to surgery, and per 24 h postoperative, respectively. Rats were sacrificed after72 hours, The tissue samples from rat esophageal were obtained for HE staining and for the measurement of RvD1, MPO, p38 MAPK, p22 phox and TLR4 levels by ELISA.Results: The severity of macroscopic esophagitis was consistent with the microscopic results, which presented from mild to severe in the order from DHA group,DMSO group, DHA +BOC-2 group to BOC-2 group. The grades of esophageal mucosal inflammation were mainly 0(5/9) or I(3/9) in DHA group, II in DMSO group(5/9),and III in DHA + BOC-2 and BOC-2 groups(5/8 and 7/7, respectively). Numerous PMN's were seen microscopically. Macroscopic esophagitis grades were higher in DHA and DMSO groups than ther other two groups(p < 0.05), while no difference was found between BOC-2 and DHA+BOC-2 groups(p > 0.05).The RvD1 levels werer decreased from DHA group, DHA + BOC-2 group, DMSO group to BOC-2 group,while no difference was found between DHA group and DHA + BOC-2 group or between DMSO group and BOC-2 group(p > 0.05).The expression of MPO, p38 MAPK,p22phox and TLR4 increased from DHA group, DMSO group, DHA + BOC-2 group to BOC-2 group(p < 0.05), while significant difference was found.between DHA and DMSO groups(p < 0.05) but not between DHA + BOC-2 and BOC-2 groups(p > 0.05).Negative correlation was found among RvD1 and MPO, p38 MAPK, p22 phox and TLR4(r=-0.69,-0.76,-0.67 and,-0.55, respectively, p <0.05), while a positivecorrelation was found Between P22 phox and TLR4 expresion(r=0.55, p<0.05).Conclusion: Antagonizing RvD1 receptor attenuated the protective effects of DHA in mucosal inflammation of RE, which suggests that RvD1 may play a key role on RE rats accepting DHA intervention.and the potential mechanisms may include the suppressing the phosphorylation of P38 MAPK, inhibition of toll receptor's signal pathway expression and oxidase activity..