【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。更多还原

【Abstract】 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.更多还原