The role of epidermal growth factor in multiple organ dysfunction of mice

Objective To study the role of recombinant human epidermal growth factor (rhEGF) in the prognosis of multiple organ dysfunction syndrome (MODS) in mice. Methods One hundred and twenty clean male Kunming mice were randomly ( random number) divided into normal saline control group (n =15),MODS model control group (n =15) and MODS + rhEGF treatment group (n =90).The MODS models were made by using Caballero ME method with thioacetamide (TAA) 2000 mg/kg injected intraperitoneally to establish monophasic rapid onset pattern of MODS model in mice.MODS + rhEGF treatment group was further randomly divided into two subgroups,namely intraperitoneal injection group (n =45 ) and subcutaneous injection group (n =45 ).Each subgroup was divided again into three small subgroups (n =15) as per different doses of rhEGF used,namely 10 μg/kg,30 μg/kg and 50 μg/kg.Within 24 hours after modeling,the respiration,body weight,food eaten and general physical changes were observed.Mortality was calculated 24 hours after modeling.After the animals sacrificed,the tissues of viscus including liver,kidney,heart,brain,lung,spleen,pancreas,intestine and stomach were collected immediately.The histological changes of visceral tissues were studied by using hematoxylin -eosin staining under the light microscope.All the experimental data were presented in,and body weight changes were compared using t-test,and after different routes of administration with different doses of rhEGF used in MODS,the mice body weight changes were analysed by using the Dunnett method,and the mortalities of mice were compared by using Fisher exact test,and P ＜ 0.05 was considered statistically significant difference. Results There was no significant difference in mortality betweeu mice in rhEGF subcutaneous administration group and MODS model control group (P ＞ 0.05 ),but the total mortality of hrEGF MODS intraperitoneal administration group (6.7％ in dose of 50 μg/kg and 20％ in dose of 30 μg/kg) was significantly lower than that of MODS model control group (73.3％) ( P ＜ 0.05 ) and the mortality of mice treated with intraperitoneal 50μg/kg rhEGF (6.7％ ) was lower than that treated with 10μg/kg rhEGF (P=0.014).The mortality of mice in rhEGF MODS (50 μg/kg ) intraperitoneal administration group was significantly lower than that in subcutaneous administration group (40％) (P =0.031 ), The histopathological changes in rhEGF MODS treatment group were not as remarkable as seen in mice of control group.The histopathological changes were dose - dependent.The higher doses of rhEGF,the lesser hepatic congestion,liver cell apoptosis,hepatic cell cloudy swelling and cell vacuolization.Similarly,as RhEGF dosage increased,pulmonary interstitial congestion,inflammatory cells and apoptotic bodies reduced,and bronchial ciliated columnar epithelium less shed.Conclusions RhEGF plays a positive role in repairement of tissue damage in TAA - induced MODS murine model.The rhEGF given by intraperitoneal route of administration is more effective to reduce the 24 h mortality of MODS mice than that by subcutaneous route. Key words: Recombinant human epidermal growth factor; Thioacetamide; Multiple organ dysfunction syndrome; Intraperitoneal injection; Subcutaneous injection; Mortality