Study On Anti-radiation Effect Of Keratinocyte Growth Factor In A Mouse Model

ObjectiveTo investigate the protective effect of KGF (keratinocyte growth factor) on mice irradiated by7.2Gy y ray and then do some research on the mechanism. The purpose of our research is to provide an important theoretical basis for KGF therapy on acute radiation sickness.MethodsC57BL/6mice were selected to receive whole body irradiation of137CS y ray to build a mouse model of acute radiation sickness. The C57BL/6J mice were randomly divided into five groups:control group, simple IR (irradiated) group and low, middle, high dose groups of KGF. Pretreated with KGF, test the protective effects on the DNA damage in irradiated mice by the SCGE(single cell gel electrophoresis) and micronuclei assay,include the indexes of the comet tail DNA percentage, tail length, tail moment, Olive tail moment in peripheral blood and cells micronucleus rate, PCE/NCE values in bone marrow cells.Treated with KGF, test the protective effects on intestinal injury in irradiated mice by observing the general situation in mice, protein concentration and the NO content of mice intestinal tissue, intestinal tissue section HE staining pathology analysis and so on.ResultsTest the indexes of the comet tail DNA percentage, tail length, tail moment, Olive tail moment of peripheral blood in a mouse model,compared with simple IR group,low dose group of KGF is no significant difference,middle dose group of KGF is significant difference,high dose group of KGF is more significant difference. Test cells micronucleus rate, PCE/NCE values in bone marrow cells in a mouse model,compared with simple IR group,three dose groups of KGF show cells micronucleus rate decrease and PCE/NCE values rise,difference is definitely.After irradiation, irradiated four groups are different degrees of hair scattered, gloss reduction, listlessness, decreased activity, eating and drinking water in quantity, compared with simple IR group,three KGF groups of mice is better.Record weight changes of each experimental group after irradiation, the results show that before irradiation, weight average of different groups mice is less than0.6g, after irradiation, irradiated four groups began to appear weight decreased obviously on the first day after irradiation, and three KGF groups appear the lowest weight on the fourth day after irradiation,then weight recovery, simple IR group appears the lowest weight on the seventh day after irradiation, recovery is not obvious.Test protein concentration and the NO content of mice intestinal tissue of each experimental group after irradiation, compared with simple IR group, three KGF groups show that the protein concentrations significantly increase, high dose of KGF group is significant difference; NO content of both middle and high dose group of KGF decreased obviously.Observe the pathological change of intestinal tissue, analysis morphologic change of villi and crypt of each group, injury of simple IR group is heavier, the small intestinal mucosa structure damage, visible flake bleeding, mucosal edema, part of the villi fall off, crypt destruction; low dose group of KGF shows that small intestine tissue mucosa edema, villi and crypt are complete, no other changes such as hemorrhage and necrosis; middle dose group of KGF shows that small intestine tissue mucosa mild edema, villi and crypt are complete, no other changes such as hemorrhage and necrosis; high dose group of KGF shows no obvious change.ConclusionKGF has significant genetic protection, can promote the repair of DNA damage, also can reduce bone marrow suppression induced by radiation, KGF can effectively reduce intestinal tissue injury induced by radiation, then we dan speculate that KGF can prevent or reduce the occurrence of all kinds of radiation sickness and is expected to become new type of drug to protect and control radiation damage, but the protective mechanism is not clear, need further research.