二维斑点追踪显像(STI)评价硫酸吲哚酚(IS)对肾功能不全(CRF)大鼠的心脏毒性

Assessment of indoxyl sulfate (IS)-induced cardiotoxicity in rats with chronic renal failure (CRF) by speckle tracking imaging (STI)

目的采用二维斑点追踪显像(speckle tracking imaging,STI)技术评价硫酸吲哚酚(indoxyl sulfate,IS)在肾功能不全(chronic renal failure,CRF)大鼠模型中的心脏毒性。方法方法30只6周龄SD大鼠,随机入组肾功能不全CRF手术对照组、CRF+IS处理(IS)组和假手术(sham operation,SOR)组,每组10只。对CRF组和IS组实施5/6肾切除术建立肾功能不全模型,建模成功后,IS组给予隔天腹腔注射IS(100 mg/kg)约24周。每组大鼠在基线和注射结束1周时采集左室短轴二维超声图像,分析获得应变及应变率参数并进行组间及组内比较。实验完成后取心脏标本行病理学检查。结果IS组中3只大鼠在IS注射12~20周中发生猝死,实验结束时SOR组10例,CRF组10例,IS组7例纳入统计分析。3组的左室内径均较基线明显增大,IS组和CRF组的室壁厚度均较基线明显增厚,IS组肥厚程度更为显著(P均<0.01)。实验前后,径向应变(radial strain,RS)在CRF组显著增加(P=0.017),但在IS组及SOR组差异无统计学意义。舒张功能参数环向应变率(circumferential peak E’/peak/A’,E’/A’-SRc)和径向应变率(radial peak E’/peak/A’,E’/A’-SRr)在IS组和CRF组均较基线显著降低,且实验后IS组显著低于CRF组(P均<0.01)。CRF组及IS组的心脏重量均显著大于SOR组(P均<0.05)。心肌细胞面积在SOR组、CRF组及IS组依次增大,且心肌纤维化程度在SOR组、CRF组和IS组依次增加(P均<0.05)。结论IS可以加重肾功能不全大鼠的心肌损害,表现为心肌细胞的肥厚,坏死和纤维化,且左室舒张功能的下降早于收缩功能受损,应变率显像的舒张功能指标可敏感检测IS导致的左室舒张功能改变。

Objective To investigate the cardiotoxicity of indoxyl sulfate(IS)in a chronic renal failure(CRF)rat model by speckle tracking imaging(STI).Methods Thirty SD rats aged 6 weeks were divided into 3 groups,including CRF group,CRF+IS group and sham operation(SOR)group(n=10 for each).The 5/6 nephrectomy was performed on CRF and IS groups to build CRF model.After modeling success,IS group was given intraperitoneal injection of IS(100 mg/kg)every other day for up to 24 weeks.Echocardiography was performed at baseline and 1 week after the end of IS treatment.Strain and strain rate of left ventricular short axis were compared between-group and intra-group based on STI analysis.After the experiment,the heart specimens were taken for pathological examination.Results Sudden death occurred in 3 rats in IS group during 12-20 weeks of IS injection.At the end of the experiment,10 cases in SOR group,10 cases in CRF group and 7 cases in IS group were included in the statistical analysis.Left ventricular end-diastolic diameter(LVEDD)was enlarged in all the 3 groups.Left ventricular wall thickness(LVWT)was increased in IS group and CRF group and the increases were more notable in IS group(all P<0.01).Radial strain(RS)was increased in CRF group(P=0.017),while no significant difference was found in IS group and SOR group compared with the baseline data.Both circumferential peak E’/peak A’(E’/A’-SRc)and radial peak E’/peak A’(E’/A’-SRr)decreased in CRF group and IS group,and the decreases were more significant in IS group compared with CRF group(all P<0.01).The heart weights were increased in CRF group and IS group compared with SOR group(all P<0.05).Histological analysis showed myocardial hypertrophy,necrosis,fibrosis happened in CRF and IS group,and the areas of myocardial cells were in ascending order of SOR,CRF and IS groups(all P<0.05).Conclusions IS exposure can aggravate myocardial hypertrophy,necrosis and fibrosis in CRF rats.Left ventricular diastolic dysfunction happened earlier than systolic dysfunction.Left ventricular diastolic functional parameters provided by STI could sensitively detect IS-induced myocardial injury.