Objective:To investigate the expression and effect of epidermal growth factor(EGF) on a rat model with colonic hypersensitivity induced by acetic acid. Methods:A total of 20 neonatal male rats were included in this study. Rat models with colonic hypersensitivity(n = 10) were established by intra-colonic infusion of 0.5% acetic acid(AA) at the age of 10~21 days,the controls(n = 10) received the same volume saline. Abdominal withdrawal reflex(AWR) score and external oblique muscle electromyography(EMG) activities were detected after colorectal expansion(CRD) stimulation to evaluate visceral sensitivity. The levels of EGF and 5-HT in plasma and intestinal tissues were measured by enzyme-linked immunosorbent assay(ELISA). The expression of serotonin transporter (SERT) was determined by Western blot to analyze the relationship between EGF levels and SERT expression in colon tissues. To further confirm the influence of EGF on SERT,rat intestinal epithelial cells (IEC-6) were stimulated at various concentrations of EGF (0,20,40 and 80 ng/ml) for 24 h to examine SERT protein expression. Results:Compared with the control rats,the AWR scores and EMG curve area during CRD in the rats with high colonic hypersensitivity were significantly increased (P < 0.05). HE staining and MPO level detection showed that no inflammation was found in both groups,which indicated that visceral hypersensitivity was successfully established. For visceral sensitized rats,the expression of SERT protein in colon were lower than that in the control group (0.711 ± 0.219 vs 0.980 ± 0.239,P < 0.01),and the levels of EGF in plasma[(2.639 ± 0.107)ng/ml vs(4.066 + 0.573)ng/ml,P < 0.05] and colonic tissues [(3.244 ± 0.135)ng/100 mg vs(3.582 + 0.197)ng/100 mg,P < 0.05] were also decreased compared with the controls. The concentrations of 5-HT in plasma and colonic tissues of model rats were significantly increased compared with those of the controls [(6.125 ± 0.534)ng/ml vs(3.540 ± 0.442)ng/ml,(5.527 ± 0.514)ng/100 mg vs(2.650 ± 0.495)ng/100 mg,respectively in plasma and colon,P < 0.05]. Furthermore,we analyzed the relationship between EGF and SERT level in colon tissues,and found that they were positively correlated (r = 0.820,P < 0.001). In vitro,IEC-6 cells were treated with EGF at different concentration (0,20,40 and 80 ng/ml) for 24 h. Compared with the concentration of 0 ng/ml,the relative expression of SERT was significantly increased (1.398 ± 0.091,1.725 ± 0.124 and 1.571 ± 0.088 at 20,40 and 80 ng/ml,respectively,P < 0.05). Conclusion:In visceral hypersensitivity rats,the EGF levels both in plasma and colonic tissue were decreased,but the 5-HT concentrations were increased. Moreover,the expression of SERT protein was positively correlated with EGF levels in colonic tissue. EGF can up-regulate the expression of SERT protein in IEC-6 cells in dose-dependent manner. These suggest that EGF may be involved in the formation of visceral hypersensitivity by affecting SERT expression.