Experimental Study On The Protective Mechanism Of Amifostine On Microvascular Damage Induced By Radiation Enteritis In Mice

ObjectiveTo study the effect and significance of amifostine on the expression of PI3K/PKB pathway and its related genes VEGF,b FGF and NF-κB pathway and its related genes VCAM-1,ICAM-1 in the small intestine of mice with radiation enteritis.To explore the protective mechanism of amifostine against radiation-induced enteritis microvascular injury and the mechanism of clinical "vascular clustering" sign formation.MethodsThe mice were divided into control group,experimental group and amifostine intraperitoneal injection group.After 6Gy 60Coγ-ray systemic irradiation,the pathological changes were observed in batches at the 1th day,7th day,14 th day,21 th day,28 th day and 90 th day.The q RT-PCR method was used to detect the relative expression of PI3K/PKB pathway and its related genes VEGF,b FGF and NF-κB pathway and its related genes VCAM-1,ICAM-1in control,experimental and intervention groups at different time points.ResultsIn the acute phase of radiation enteritis,the submucosal microvascular injury was obvious in the experimental group and the intervention group.The injury in the intervention group was lighter than that in the experimental group.In the chronic phase,microvessel occlusion,abnormal dilatation of blood vessels,and fibrosis were seen in the submucosa of the small intestine in theexperimental group.This is consistent with the pathological characteristics of the clinical "vascular clustering" sign.The above-mentioned phenomenon was not seen in the intervention group,and the tissue repair was significantly better than that in the experimental group.On the first day after irradiation,the relative m RNA expression of the PI3K/PKB pathway and its related genes VEGF,b FGF,NF-κB pathway and its related genes VCAM-1,ICAM-1 in the small intestine of the experimental group were significantly increased(P<0.05).On the 7th day,the expression of each gene in the radiation group showed a downward trend but was still higher than the control group(P<0.05).On the 14 th and 21 st days,the expressions of VEGF and b FGF genes were still higher than those of the control group(P<0.05),and the relative m RNA expression of other genes decreased to control level(P>0.05).On the 28 th day,the expression of each gene was not statistically different from the control group(P>0.05).The relative expression levels of all genes m RMA in the intervention group were significantly increased on the first day after irradiation(P<0.05).On the 7th day,the relative expression of NF-κB m RNA was significantly lower than that of the experimental group but still higher than that of the control group(P<0.05).The expressions of other genes were all reduced to the control group level(P>0.05).On the 14 th,21st,and 28 th days,expression of each gene was not statistically different from the control group(P>0.05).Compared with the experimental group,the m RNA expression of each gene at different time points was different in the intervention group,the relative expression was reduced,and the change trend was different(P<0.05).ConclusionsIn the acute phase of radiation enteritis,PI3K/PKB pathway and its related genes VEGF,b FGF and NF-κB pathway and its related genes VCAM-1,ICAM-1m RNA expression are up-regulated,which may play a role in microvascular injury after radiation.Amifostine may protect microvessels by down-regulatingthe expression of these genes,thereby reducing radiation damage.The vascular injury and actication of fibrosis at acute phase may lead to formation of "vascular clustering" signs at chronic stage.