斑点追踪技术在达格列净改善蒽环类药物所致小鼠心脏毒性中的应用研究  

Study on dapagliflozin in improving cardiotoxicity induced by anthracyclines in mice with speckle tracking technique

作　　者：毕亮亮[1] 赵红梅[2] 李成 李瑞[4] 尚丽娜 邸桂新[1] 赵金惠[1] BI Liangliang;ZHAO Hongmei;LI Cheng;LI Rui;SHANG Lina;DI Guixin;ZHAO Jinhui(Department of Ultrasound Diagnosis,Affiliated Hospital of Hebei University,Baoding 071000,China;Department of Geriatrics,Affiliated Hospital of Hebei University,Baoding 071000,China;Physical Examination Center,Affiliated Hospital of Hebei University,Baoding 071000,China;Department of Obstetrics,Affiliated Hospital of Hebei University,Baoding 071000,China)

机构地区：[1]河北大学附属医院超声诊断科,河北保定071000 [2]河北大学附属医院老年医学科,河北保定071000 [3]河北大学附属医院体检中心,河北保定071000 [4]河北大学附属医院产科,河北保定071000

出　　处：《医学研究与教育》2024年第2期1-8,共8页Medical Research and Education

基　　金：河北省科技厅基金项目(19277761D);河北省医学科学研究重点课题(20180725)。

摘　　要：目的探讨斑点追踪技术在评估达格列净改善蒽环类药物所致小鼠心脏毒性的可行性。方法将BALB/c雄性小鼠随机分为对照组、表柔比星组和达格列净干预组。达格列净在表柔比星用药前连续给药3 d,然后每间隔1 d给药1次,持续3周(给予10 mg/kg达格列净,灌胃)。表柔比星(3 mg/kg,腹腔注射)或等体积0.9%氯化钠溶液每4天注射1次,持续3周。分别于基线、第3周期化疗后和最后一周期化疗后1 d行常规超声心动图检查和基于斑点追踪技术左心室整体纵向应变(global longitudinal strain,GLS)测量。实验结束后,通过组织学分析评估心肌损伤。结果与对照组和达格列净干预组比较,表柔比星组表现出明显的心肌细胞结构异常,胶原蛋白含量和心肌细胞凋亡百分比增高。心脏功能方面,表柔比星组在第3周期注射后GLS显著降低(P<0.05),并且随着累积剂量的增加,GLS持续下降(P<0.05);达格列净干预组GLS只在最后一周期化疗结束后表现为轻微减低,但差异无统计学意义(P>0.05)。此外,GLS与心肌病理损伤表现出良好的相关性,且与胶原蛋白含量相关性最高(r_(s)=-0.637,P<0.001)。结论达格列净干预治疗后可明显改善化疗小鼠的心脏损伤;GLS在评估接受心脏保护性药物后的心功能改善方面是可行的。Objective To investigate the feasibility of speckle tracking technique in evaluating the improvement of cardiotoxicity induced by anthracyclines with dapagliflozin.Methods Male BALB/c mice were randomly divided into normal control group,epirubicin group and epirubicin plus dapagliflozin group.Dapagliflozin were administered at three consecutive days before epirubicin treatment,followed by once every other day for 3 weeks(10 mg/kg,p.o.).Epirubicin(3 mg/kg,i.p.)or an equal volume of 0.9%sodium chloride solution were injected every 4 days for 3 weeks.Conventional echocardiography and measurement of left ventricular global longitudinal strain(GLS)based on speckle tracking technique were performed at baseline,one day after the third Epi dosage and one day after the last chemotherapy.Myocardial damage were evaluated by histological analysis at the end of experiment.Results Compared with control group and epirubicin plus dapagliflozin group,epirubicin group showed significant abnormalities in myocardial cell structure,and an increase in collagen content and percentage of myocardial cell apoptosis.In terms of cardiac function,GLS decreased significantly after the third injection in epirubicin group(P<0.05),and GLS continued to decrease with increasing cumulative dose(P<0.05).GLS only showed slight decrease in epirubicin plus dapagliflozin group after the last chemotherapy,but this difference was not statistically significant(P>0.05).In addition,there was a good correlation between GLS and myocardial pathological damage,with collagen content showing the highest correlation(r_(s)=-0.637,P<0.001).Conclusion Dapagliflozin can significantly improve the heart damage caused by epirubicin in the mouse model.GLS is feasible for evaluating heart function improvement after receiving cardioprotective drugs.

关 键 词：斑点追踪 达格列净 蒽环类药物 心脏毒性 

分 类 号：R969[医药卫生—药理学]