心肺联合超声对阿霉素诱导心力衰竭大鼠疾病进展和疗效的评价作用

Evaluation of cardiopulmonary ultrasound on progression and efficacy of doxorubicin-induced heart failure in rats

  • 摘要: 目的:探讨心肺联合超声(CPUS)对阿霉素(DOX)诱导心力衰竭(HF)大鼠疾病进展和治疗效果的评价作用。方法:将88只SD大鼠随机分为对照组(n=8)、模型组(n=48,腹腔注射DOX,2次/周)和治疗组(n=32,DOX注射6周后给予芪苈强心颗粒灌胃,1 次/d)。模型组根据DOX注射时间长短(1~6周)分为6个亚组,每组8只。治疗组根据灌胃时间长短(1~4周)分为4个亚组,每组8只。各组均行CPUS检查及病理组织学检查。结果:与对照组比较,模型组左房室增大,收缩末期左房横径(LAD)、收缩末期左房横径/收缩末期左房横径(LAD/RAD)、舒张末期左室横径/舒张末期右室横径(LVEDD/RVEDD)升高,左、右室E/e’和右室壁厚度(RVWT)升高,左心室射血分数(LVEF)、三尖瓣环收缩期位移(TAPSE)和左室壁厚度(LVWT)降低(均P<0.05);模型组胸膜线、A线模糊或消失,B线数量增多,肺部超声评分(PLUS)高于对照组。苏木精—伊红(HE)染色显示,模型组心脏病理表现为心肌细胞变性水肿,心肌纤维排列紊乱,间质水肿疏松,炎症细胞浸润;肺组织病理表现为肺泡结构破坏,小叶间隔增厚,肺泡腔积液,肺泡毛细血管淤血,炎症细胞浸润,符合心力衰竭的心、肺病理改变。治疗组左房室减小,LAD、LVEDD/RVEDD低于模型组(P<0.05),LAD/RAD差异无统计学意义(P>0.05);左、右室收缩及舒张功能改善,LVEF、TAPSE高于模型组,左、右室E/e’低于模型组(P<0.05);LVWT高于对照组,右室壁厚度(RVWT)低于对照组(P<0.05);肺部超声表现为B线数目减少,可见A线。与模型组注射6周比较,治疗组给药3周、4周PLUS评分显著降低(P<0.05),心、肺病理形态随着给药时间延长而逐渐改善。心脏超声参数与PLUS具有显著相关性,LAD、LVEDD/RVEDD与PLUS呈正相关关系,LVEF、TAPSE与PLUS呈负相关关系(P<0.001)。结论:CPUS能够动态监测HF大鼠的疾病进展,评价干预治疗效果,能密切追踪病程发展,可望为HF相关基础研究和临床治疗提供有效监测方法。

     

    Abstract: Objective: To explore the evaluation effect of cardiopulmonary ultrasound (CPUS) on the progression and efficacy of doxorubicin (DOX)-induced heart failure (HF) rats. Methods: Eighty-eight SD rats were randomly divided into three groups: control group (n=8), model group (n=48, intraperitoneal injection of DOX, twice a week), and treatment group (n=32, 6 weeks after DOX injection, Qili Qiangxin Capsules were given intragastric administration, once a day). The model group was divided into 6 subgroups with 8 rats in each group according to the duration of DOX injection (1-6 weeks). The treatment group was divided into 4 subgroups with 8 rats in each group according to the duration of intragastric administration (1-4 weeks). CPUS and histopathological examination were performed in all groups. Results: Compared with the control group, the left atrioventricular chamber in the model group enlarged; the left atrial diameter (LAD) at the end of the contraction, the ratio of left atrial diameter to right atrial diameter (LAD/RAD) at the end of the contraction, and the ratio of left ventricular end-diastolic diameter to right ventricular end-diastolic diameter (LVEDD/RVEDD) were all higher than those in the control group; the E/e’values of both the left and right ventricles were increased; the left ventricular ejection fraction (LVEF) and the tricuspid annular plane systolic excursion (TAPSE), and the left ventricular wall thickness (LVWT) were decreased (all P<0.05). In the model group, the pleural line and A-lines were blurred or disappeared, the number of B-lines was increased, and the lung ultrasound score (PLUS) was higher than that of the control group. HE staining showed that the histopathological changes in the heart of the model group were myocardial cell degeneration and edema, with disordered myocardial fiber arrangement, interstitial edema and porosity, and inflammatory cell infiltration. The histopathological changes in the lung tissue were destruction of alveolar structure, thickening of lobular septa, effusion in alveolar cavity, congestion of alveolar capillaries, and inflammatory cell infiltration, which were consistent with the histopathological changes of heart and lung in HF. In the treatment group, the left atrioventricular chamber was decreased, LAD and LVEDD/RVEDD were lower than those in the model group (P<0.05), while there was no statistically significant difference in LAD/RAD (P> 0.05). The systolic and diastolic functions of the left and right ventricles were improved, LVEF and TAPSE were higher than those in the model group , and the E/e’values of both the left and right ventricles were lower than those in the model group (P<0.05). LVWT was higher than that in the control group, while RVWT was lower than that in the control group (P<0.05). The lung ultrasound showed a decrease in the number of B-lines, and Alines were visible. Compared with the model group injected for 6 weeks, the PLUS score of the treatment group was significantly lower after 3 and 4 weeks of injection (P<0.05), and the pathological morphology of the heart and lung gradually improved with the extension of the administration time. There was a significant correlation between cardiac ultrasound parameters and PLUS. LAD and LVEDD/RVEDD were positively correlated with PLUS, while LVEF and TAPSE were negatively correlated with PLUS (P<0.001). Conclusion: CPUS can dynamically monitor the disease progression of HF rats, evaluate the effectiveness of intervention and treatment, and closely track the progression of the disease, which is expected to provide effective monitoring methods for basic research and clinical treatment of HF.

     

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