低剂量电离辐射对糖尿病小鼠肾脏ICAM-1 mRNA和蛋白表达的影响

Effects of low dose radiation on expressions of ICAM-1 mRNA and protein in kidney of diabetic mice

目的:研究低剂量电离辐射(LDR)对链脲佐菌素(STZ)诱导的1型糖尿病(DM)小鼠肾脏细胞间黏附分子-1(ICAM-1)mRNA及蛋白表达的影响,阐明LDR抗炎作用可能是其治疗糖尿病的主要机制。方法:选取健康适龄C57BL/6J小鼠,分为4组(对照、DM、LDR和DM/LDR组)。其中DM与DM/LDR组经腹腔注射STZ,建立DM模型,另2组给予等量枸橼酸溶液。造模后DM/LDR与LDR组给予25mGy隔日照射,共照射4周。在照射后2、4、8、12及16周,利用RT-PCR及Westernblotting方法检测其肾脏ICAM-1mRNA及蛋白表达。结果:小鼠造模后照射前各组肾脏总ICAM-1mRNA及蛋白表达差异无显著性(P>0.05)。给予LDR2周时DM组肾脏ICAM-1mRNA及蛋白表达显著高于其他3组(P<0.05)。照射后4周时DM/LDR组ICAM-1mRNA表达水平明显高于非DM组(P<0.05),但仍显著低于DM组,这种差异一直保持到照后16周。而LDR组其表达水平显著高于对照组(P<0.05)。免疫组织化学检测:与非DM组比较,DM组小鼠肾小球、肾小管结构异常,且阳性细胞染色数量明显增多。但DM/LDR组肾小球肾小管损伤较DM组有所减轻,且阳性细胞数量显著少于DM组。结论:在糖尿病状态下LDR能有效降低ICAM-1mRNA及蛋白表达水平,缓解肾脏的炎症反应;在正常机体LDR可提高免疫力,促进免疫相关因子释放,提示LDR视机体所处不同状态发挥不同的调节功能。

Objective To study the effects of low dose radiation（LDR） on the expressions of intercellular adhesion molecule-1（ICAM-1） mRNA and protein in kidney of diabetes mellitus（DM） mice and illuminate that anti-inflammation of LDR is a main mechanism for diabetic therapy.Methods The healthy and right age C57BL/6J mice were divided into 4 groups including control,DM,LDR and DM/LDR.The mice in DM and DM/LDR groups were injected intraperitoneally with streptozocin（STZ） to set up DM models.The mice in DM/LDR and LDR groups were irradiated with 25 mGy every other day for 4 weeks.The expressions of ICAM-1 mRNA and protein in kidney were detected with RT-PCR and Western blotting 2,4,8,12 and 16 weeks after irradiation.Results The expressions of ICAM-1 mRNA and protein in kidney had no significant difference among 4 groups before LDR（P〉0.05）.The expressions of ICAM-1 mRNA and protein 2 weeks after irradiation with LDR were higher than those in the other 3 groups（P〈0.05）.The expressions of ICAM-1 mRNA and protein in the DM/LDR group 4 weeks after irradiation were also significantly higher than those in non-DM groups（P〈0.05）,but still significantly lower than those in DM group（P〈0.05）,and the significant differences were kept to 16 weeks after irradiation.But the expressions of ICAM-1 mRNA and protein in LDR group were significantly higher than those in control group（P0.05）.IHC assay showed that the glomerular and tubular in DM and DM/LDR groups were abnormal and the quantities of the positive staining cells were significantly increased compared with non-DM groups.However the damage of glomerular and tubular in DM/LDR was significantly supressed compared with DM gorup and the positive staining cells were also decreased.Conclusion Under the circumstance of DM,LDR can significantly decrease the expressions of ICAM-1 mRNA and protein in mouse kidney to relief the inflammation reaction in kidney;but in normal condition,LDR can improve the immunity and promote the release of immune-related factors.It means that LDR can play different roles under different circumstance.