氨磷汀对急性放射性肠炎小鼠NF-κB通路和VCAM-1、ICAM-1基因表达的影响

Effect of amifostine on the expression of NF-κB pathway and VCAM-1、ICAM-1 gene in mice with acute radiation-induced enteritis

目的:研究氨磷汀对急性放射性肠炎小鼠小肠组织中核转录因子kappaB(NF-κB)通路和血管间粘附分子-1(VCAM-1)、细胞间粘附分子-1(ICAM-1)基因表达的影响和意义.方法:将小鼠分成对照组、实验组、氨磷汀腹腔注射干预组,采用6Gy 60Coγ-射线全身辐射,于第1、7、14天分批处死小鼠观察病理改变.实时荧光定量PCR(Q-PCR)方法检测不同时间点对照组、实验组和氨磷汀干预组NF-κB、VCAM-1、ICAM-1基因mRNA表达水平的变化.结果:辐射后实验组、干预组均可见明显黏膜下层微血管损伤,干预组损伤较实验组轻.辐射后第1天实验组、干预组小鼠小肠组织中NF-κB、VCAM-1、ICAM-1基因mRNA表达水平均显著升高(P<0.05),干预组升高水平显著低于实验组(P<0.05);第7天实验组各基因mRNA水平均呈下降趋势但仍高于对照组(P<0.05),干预组达到或接近对照组水平;第14天实验组、干预组各基因mRNA表达水平与对照组比较无统计学差异(P>0.05).结论:急性放射性肠炎早期即发生NF-κB、VCAM-1、ICAM-1基因mRNA的表达上调,可能在辐射后微血管损伤中发挥作用,氨磷汀可能通过下调上述基因表达对微血管起到保护作用.

Objective:To study the effect and significance of amifostine on the expression of NF-κB pathway and VCAM-1、ICAM-1 gene in small intestinal tissues of mice with acute radiation-induced enteritis.Methods:The 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,the 7th day and 14th day.The expressions of NF-κB,VCAM-1 and ICAM-1 gene mRNA in the control group,experimental group and amifostine intervention group were detected by Q-PCR.Results:After irradiation,the submucosal microvascular injury was observed in the experimental group and the intervention group.The injury in the intervention group was lighter than that in the experimental group.The 1th day after irradiation,the mRNA levels of NF-κB,VCAM-1 and ICAM-1 gene in the small intestine of the experimental group and the intervention group were significantly increased(P<0.05),and the elevated level of the intervention group was significantly lower than that of the experimental group(P<0.05).The 7th day after irradiation,the mRNA level of each gene in the experimental group showed a downward trend but still higher than the control group(P<0.05).The intervention group reached or approached the level of the control group.The 14th day after irradiation,the mRNA expression levels of the genes in the experimental group and the intervention group were not different from those in the control group(P>0.05).Conclusion:The expression of NF-κB,VCAM-1 and ICAM-1 mRNA is up-regulated in the early stage of acute radiation,which may play a role in microvascular injury after irradiation.Amifostine may protect microvessels by down-regulating the expression of these genes.