摘要:
目的 探讨抗凝血酶Ⅲ对造影剂肾病(CAN)的保护作用,并对其可能机制进行探讨.方法 根据文献方法建立CAN动物模型,将24只大鼠随机分为对照组(注射等量生理盐水,不造模),模型组(仅造模,不给药),抗凝血酶Ⅲ造模前干预组(于造模前30 min尾静脉注射抗凝血酶Ⅲ),以及抗凝血酶Ⅲ造模后干预组(于造模后30 min尾静脉注射抗凝血酶Ⅲ),每组6只.检测各组大鼠的肾脏功能,以及肾脏炎症反应、氧化应激、细胞凋亡和肾血流情况.结果 与对照组相比,模型组大鼠肾功能损伤和病理损伤明显加重(P<0.01).与模型组相比,造模前干预组和造模后干预组的BUN和SCr水平均有明显下降(P< 0.05或P<0.01);造模前干预组MDA水平有所降低,SOD水平有所上升,而造模后干预组仅MDA水平有所降低(P< 0.05或P<0.01);造模前干预组TNF-α、MCP-1和ICAM-1的mRNA表达水平均较模型组有所降低(P<0.01),造模后干预组仅TNF-α的mRNA表达水平有所下降(P<0.05);免疫染色分析显示,与模型组相比,造模前干预组和造模后干预组的F4/80阳性巨噬细胞浸润程度明显减轻(P<0.05);蛋白质印迹法结果显示,与模型组相比,造模前干预组cleaved caspases-3的表达有所下降,Bcl-2表达升高(P<0.05),但造模后干预组仅cleaved caspases-3的表达下降(P<0.05);彩色多普勒超声结果表明,造模前干预组和造模后干预组的肾脏血流灌注减少现象可明显缓解.结论 抗凝血酶Ⅲ可改善造影剂所致肾损伤,且预防性用药效果更佳.其作用机制可能与降低肾脏组织的炎症反应,抑制氧化应激,增加肾血流量以及减少肾脏细胞凋亡有关.%Objective To investigate the protective effect of antithrombin Ⅲ on contrast associated nephropathy (CAN) and its possible mechanism.Methods According to the literature method,the CAN animal model was established.A total of 24 rats were randomly divided into 4 groups (n=6 each),such as control group (normal saline injection,no modeling);model group (only modeling,no medicine intervention);antithrombin Ⅲ pre-modeling intervention group (intravenous injection antithrombin Ⅲ at 30 min before modeling);and antithrombin Ⅲ post-modeling intervention group (intravenous injection antithrombin Ⅲ at 30 min after modeling).The renal function,renal inflammation,oxidative stress,apoptosis and renal blood flow condition in each group were detected.Results Compared with the control group,the renal function and pathological damage of model group were significantly increased (P<0.01).Compared with the model group,the levels of BUN and SCr in pre-modeling intervention group and post-modeling intervention group were significantly decreased (P<0.05 or P<0.01).In pre-modeling intervention group the MDA level was decreased and the SOD level was increased,while only the MDA level in post-modeling intervention group was decreased (P<0.05 or P<0.01).Compared with model group,the TNF-α,MCP-1 and ICAM-1 mRNA expression levels in pre-modeling intervention group were decreased (P<0.01),while only the TNF-α mRNA expression level in post-modeling intervention group was decreased (P<0.05).Immuno-histochemical staining analysis showed that the F4/80 positive macrophage infiltration in pre-modeling intervention group and postmodeling intervention group was significantly reduced (P<0.05).The western blot result showed that the expression of cleaved caspases-3 in the pre-modeling intervention group was decreased and the Bcl-2 expression increased (P<0.05).But the cleaved caspases-3 expression in post-modeling intervention group was decreased (P<0.05).The Doppler ultrasound result showed that the renal blood perfusion reduction was significantly relieved in the pre-modeling intervention group and post-modeling intervention group.Conclusion Antithrombin Ⅲ can improve the renal injury induced by contrast media.The mechanism may be related to the reduction of inflammatory reaction,the inhibition of oxidative stress,the increasing of renal blood flow and the reduction of renal apoptosis.