| ObjectivesTo determine the the protective effect and possible mechanism of exogenous EGF on ischemia-reperfusion induced intestinal injury.Materials and methods80 Wistar rats were subjected to superior mesenteric artery (SMA) followed by reperfusion. Animals were randomly divided into four groups, namely sham operated control(C), ischemia group(I), ischemia-reperfusion group(R) and EGF treated group(E). In group R and E they were intravenously injected with EGF(100p,g/kg) or saline after 45 minutes of SMA occlusion and killed after 2, 6, 12 or 24 hours of reperfusion respectively. Plasma D-lactate concentrations, plasma and tissue DAO activity and organ function parameters were determined. Tissue EGF and EGF mRNA expression were measured by RT-PCR. Intestine tissue samples were also taken for histological analysis and immunohistochemical analysis of EGFR, PCNA, c-fos, c-jun, phospho-p44/42 MAPK, phospho-SAPK and phospho-p38.Main results and conclusions1. The changes of histological structure, plasma D-lactate, plasma and tissue DAO activity, gut organ function parameters and bacterial translocation indicated that the intestinal barrier was damaged after intestinal I/R injury. EGF treatment significantly improved the outcome.2 The expression of intestinal EGF mRNA and EGFR mRNA increased after ischemia and reperfusion. The former reached its peak after 6h of reperfusion and the latter at 12h. They remained higher till after 24h. EGF treatment augmented these trends.2. The expression of EGFR did not change after ischemia and in the early period of reperfusion, but increased with the time. The expressions in group E were stronger than those in group R.3. Ischemia significantly increased the number of PCNA positive cells in the the crypts. It decreased with time of reperfusion, but the cells located at the lower parts of crypts remained positive. In group E its expression were stronger.4. The expressions of c-jun were stronger than those of c-fos. They were significantly improved by ischemia and reperfusion and reached their peaks at 12h. EGF injection weakened their expression.5. phospho-p44/42 MAPK positive cells were found in intestinal villus and crypts of control and I/R insulted rats. They increased in group I and R, but more significantly in group E.phospho-SAPK. were poorly expressed in all groups. I/R insult moderately increased its expression. It was relatively higher after 12h of reperfusion and weaker in group E.In group C and I each crypt contained 5-6 phoshho-p38 positive cells which were mainly located in the lower region of crypts, as was consistent with the distribution of intestinal stem cells. The percent of positive cells in crypts increased with the time of reperfusion and reached its peak at 12 hours of reperfusion. EGF treatment brought forward its expression. 7. Results of the present study may provide some significant information for clinical treatment strategies and further research in critically illness:7.1 EGF may help reduce ischemia-reperfusion induced intestinal damage, thus promoting the repair of gut injury and preventing the development of MSOF.7.2 EGF treatment may modulate the expressions of EGF mRNA and EGFR mRNA, thus accelarating gut repair process.7.3 EGF accelerated the proliferation of intestinal cells (especially stem cells), which might be intimately related with the activation of MPAK pathway. Phospho-p38 MAPK might be a possible marker of intestinal stem cell.
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