Effect Of Epidermal Growth Factor On Expression Of Interrelated Polypeptides In Experimental CDH Lungs

Purpose Infants born with Congenital diaphragmatic hernia(CDH) have high perinatal mortality rate. One of the most reasons for death is pulmonary hypoplasia. Epidermal growth factor(EGF) had been shown to accelerate lung development and maturation of lungs, but its mechanism is not clearly. Our experiment to observe the expression of epidermal growth factor receptor(EGFR), transforming growth factor β receptor 1 (TGF β R1) .thyroid transciption factor-1 (TTF-1) and surfactant protein B (SP-B) on developing lungs in the nitrofen-induced CDH Rat Model after epidermal growth factor receptor(EGF) application, and to discuss the mechanism of EFG promoting lung development in CDH and relationship of interrelated polypeptides in developing of lungs.Methods CDH was induced in fetal rats by tube feeding timed-pregnant eighteen Sprague-dawley rat mothers( vaginal smear positive=day 0, full-term=day 22) 100 mg nitrofen dissolved in 10ml of plant oil on day 8.5 of gestation. Control four rat mothers was feeded 10ml of plant oil. Then, the eighteen rats were randomly divided into two groups. CDH group(four rats):5ml of normal saline(NS) was injected intraperitoneally for each rat on day 18.5. EGF group(forteen) was divided into seven subgroups:400μg/kg,500μg/kg,600μg/kg,700μg/kg,800μg/kg, 1000μg/kg, 1200μg/kg. EGF were given for each rat of four subgroups, respectively. All fetuses were delivered by caesarean section on day 21 under the anesthesia of sodium pentobarbital. Each fetal rat was examined for the presence of dia phragmatic hernia by midline sternotomy. Lung histological and morphometrical evaluations were performed and image analysis was combined after lung processing, immunohistochemistry was used to detect the expression the EGFR, TGF β R1, TTF-1, SP-B.Results CDH were seen in 38% about fetuses. From the microscop, we see that development of fetal retented primitive alveoli in the experimental groups. There is significantly about lung-forms between CDH(+)and CDH(-) groups. It is differentabout the expression of EGFR, TGFPRI not TTF-1,SP-B between CDH(+)and CDH(-) groups with EGF application (P<0.05) . The expression of TTF-1 is not significant only between CDH(-) and CDH(+)groups with EGF application(P>0.05). There is relationship between expression of EGFR.TGF P RJ,TTF-1,SP-B in CDH(+)and CDH(-) groups. Not TGFPR, EGFR but SP-B,TTF-1 in CDH(+) is different to CDH(+) controls (P<0.05) . At the same way, in CDH(-) and CDH(+)groups with EGF application, there are expression of EGFR, TTF-1 that is different.in CDH(+) groups (P<0.05) , the expression of EGFR changed with increasing of EGF dosage (P<0.05) . There were significant about the expression of EGFR, TGF & R,SPB,TTF-1 in each groups of CDH(+), and expression of EGFR,TTF-1 in each groups of CDH(-).Conclusion Prenatal EGF can improve pulmonary hypoplasia in the nitrofen-induce CDH rat model, moreover, EGF can promote type II pneumocytes differentiation. The effect on type II pneumocytes is dose-dependent, 600ug/kg may be more suitable. EGF can improve the the expression of EGFR,SPB,TTF-1 in the CDH. TGFPRI confrontation preceding polypeptides, inhibiting ultra-development of lung, play a part in relative inhibit. In conclusion, EGF can coordinate the expression of the interrelated polypeptides by EGFR and other mechanism, as the results, promoting the development of lungs.