Acute Intestinal Injury Induced By Indomethacin And Prophylactic And Treated Effects Of Omeprazole

OBJECTIVE This study was designed to determine the intestinal injury induced by Indomethacin on SD rats and the prophylactic and treated effect of omeprazole on intestinal injury.METHOD 55 health Male S-D rats were employed in the study, rats intestinal injury were induced by Indomethacin 20mg/kg intragastdcally(i.g.).Experiment was separated to two parts according to the two different end-points:24h and 60h after Indomethacin i.g..In the 24h part,omeprazole(30mg/kg and 60mg/kg)was administrated by intraperitoneal injection at three time:0.5 hour before Indomethacin i.g.,5 hours after Indomethacin i.g.and 12 hours after Indomethacin i.g..Rats were killed at 24 hours after Indomethacin i.g..In the 60h part,omeprazole was adminstrated by intraperitoneal injection at 12 hours,24hours,36hours and 48hours after Indomethacin i.g,rats were killed at 60 hours after Indomethacin i.g..The injury index of intestine, the serum concentration of TNF-α,the intestinal content of MPO and MDA were determinationed,intestine structural changes were observed under the microscope.RESULTS(1)Model of the acute intestinal injury in rats induced by Indomethacin were set up successfully:intestinal ulcers were induced after Indomethacin i.g.,The injury index,serum concentration of TNF-α, and intestinal content of MPO and MDA of 24h model group were higher than normal control group(p＜0.01),neutrophil infiltrate was oberserved at model group intestine.Those of 60h model group were higher than 24h model group,but the serum concentration of TNF-αwas lower than 24h group.(2)The prophylactic effect of omeprazole:after omeprazole(30mg/kg and 60mg/kg)was adminstrated by intraperitoneal injection at 0.5 hour before Indomethacin i.g.,the injury index of intestine,serum concentration of TNF-αand intestinal content of MPO and MDA were lower than 24h model group(p＜0.01),the pathological changes were abated.Those index of 60mg/kg group were higher than 30mg/kg group.(3)The treated effect of omeprazole:after omeprazole (30mg/kg and 60mg/kg)was adminstrated by intraperitoneal injection at 5 hours after Indomethacin i.g.,the injury index of intestine,the serum concentration of TNF-α,the intestinal content of MPO and MDA were lower than 24h model group(p＜0.01),the pathological changes were abated.Those index of 60mg/kg group were higher than 30mg/kg group(p＜0.05).But there were not greatly different between groups of two dose omeprazole adminstrated at 12 hours after Indomethacin i.g. with 24h model group(p＜0.01),and there were not greatly different between groups of two dose omeprazole adminstrated.(4)Between the three groups:omeprazole adminstrated at 0.5 hour before Indomethacin i.g.,at 5 hours after Indomethacin i.g.and at 12 hours after Indomethacin i.g.,the injury index of intestine,the serum concentration of TNF-α,the intestinal content of MPO and MDA were lowest in the first group,and highest in the third group.(5)In 60h part,the injury index of intestine,serum concentration of TNF-αand intestinal content of MPO and MDA of multiple administer group were lower than 60h model group(p＜0.01),and those were lower than omeprazole administrated at 12 hours after Indomethacin i.g.too(p＜0.05).CONCLUSION1.Indomethacin administered by intragastric route can induce acute intestinal injury on SD rats,and this is relation to local inflammation and oxidative damage.2.Omeprazole can Prophylaxis and Treat acute small intestinal injury induced by Indomethacin.3.The protect effects of Omeprazole on Indomethacin- induced acute small intestinal injury is related to dosage,and the earlier to use Omeprazole,the effects more better.To case of the late first treatment, the protect effects of large dose Omeprazole at multiple administrate is good to single administrate.4.The protect effects of Omeprazole on Indomethacin- induced acute small intestinal injury attributed to inhibit TNF-α,a key mediators of inflammation,inhibit neutrophile infiltrating and oxidative damage.