摘要
目的研究急性缺血性卒中(AIS)小鼠静脉注射钆喷酸葡胺(Gd-DTPA)后AIS和Gd-DTPA的协同效应对肾组织钆沉积和毒性损伤的影响。方法将40只健康的C57BL/6雄性小鼠采用随机数字表法均分为AIS组和假手术组,随后每组又均分为Gd-DTPA注射亚组和生理盐水注射亚组。每组均于术后4.5 h和1 d注射。最终将小鼠分为4组:A组(AIS组+Gd-DTPA)、B组(假手术组+Gd-DTPA)、C组(AIS组+生理盐水)、D组(假手术组+生理盐水),每组10只。每组在末次注射后第1天和第28天各随机选取5只小鼠进行实验分析。采用电感耦合等离子体质谱(ICP-MS)分析钆沉积浓度;采用血清生化和病理染色分析血清肌酐(Scr)和尿酸(UA)水平、肾小管损伤评分以及系膜基质指数。2组间比较采用独立样本t检验或配对t检验;多组间比较采用双因素方差分析,组间进一步两两比较采用Tukey检验。结果末次注射后第1天和第28天,A组小鼠肾组织钆浓度均高于B组(均P<0.05),Scr和UA值、肾小管损伤评分均高于其他各组(均P<0.05);A组末次注射后第28天的系膜基质指数也高于其他各组(P<0.05)。HE染色显示A组的损伤程度最重、范围最广。此外,A组末次注射后第28天时的肾小管损伤评分较第1天降低(P<0.05)。结论AIS和Gd-DTPA的协同效应可能会增加肾组织钆沉积量以及加重肾毒性损伤。
Objective To investigate the synergistic effect of acute ischemic stroke(AIS)and Gd-DTPA on the gadolinium deposition and nephrotoxicity after intravenous injection of Gd-DTPA in a mouse model of acute ischemic stroke(AIS).Methods Forty healthy male C57BL/6 mice were randomly divided into AIS group and sham group by random number table method,and then each group was further divided into Gd-DTPA and saline injection subgroups.Each group was injected at 4.5 hours and 1 day after modeling.Finally,this experiment was divided into 4 groups(n=10):group A(AIS group+Gd-DTPA),group B(Sham group+Gd-DTPA),group C(AIS group+saline),group D(Sham group+saline).Five mice were randomly selected from each group on day 1 and day 28 after last injection for experimental analysis.The concentration of gadolinium deposition was analyzed with inductively coupled plasma mass spectrometry(ICP-MS);and the levels of serum creatinine(Scr)and uric acid(UA),tubular injury score and mesangial matrix index were analyzed with serum biochemistry and pathological staining.Independent sample t test or paired t test was performed between 2 groups,and two-way analysis of variance(two-way ANOVA)was performed among 4 groups,following by post-hoc multiple comparisons with Tukey test.Results On day 1 and day 28 after the last injection,the group A showed higher Gd concentration than the group B(all P<0.05),higher Scr and UA levels and tubular injury scores than the other groups(all P<0.05).The mesangial matrix index was increased in the group A compared to the other groups on day 28 after the last injection(P<0.05).Most severe and extensive damage was observed in the group A on HE staining.In addition,the tubular injury score in the group A on day 28 after the last injection was lower than on day 1(P<0.05).Conclusion The synergistic effect of AIS and Gd-DTPA may increase the Gd concentration and aggravate the nephrotoxicity.
作者
王伟
许晓泉
黄新鑫
姜润浩
周江
施海彬
吴飞云
WANG Wei;XU Xiaoquan;HUANG Xinxin;JIANG Runhao;ZHOU Jiang;SHI Haibin;WU Feiyun(Department of Radiology,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)
出处
《国际医学放射学杂志》
北大核心
2023年第2期136-140,共5页
International Journal of Medical Radiology
基金
国家自然科学基金青年基金(81401497)。