LY294002对扩张型心肌病大鼠模型心肌结构及心功能的影响

Effect of LY249002 on myocardial structure and cardiac function in rats with dilated cardiomyopathy

目的:探讨PI3K抑制剂LY294002对腹腔注射阿霉素诱导的扩张型心肌病(dilated cardiomyopathy,DCM)大鼠模型心肌结构及心功能的影响。方法:将52只雄性SD大鼠随机分为对照组(n=16)和模型组(n=36),模型组前6周通过腹腔注射阿霉素建立DCM大鼠模型,对照组同期腹腔注射等量的生理盐水。观察2周后(8周末)每组随机处死6只存活大鼠;9~16周将建模成功的24只模型大鼠随机分为DCM组(n=12)和LY294002组(n=12),分别予以生理盐水和LY294002,16周末处死所有存活大鼠。8周末及16周末,所有存活大鼠行血浆氨基末端脑钠肽前体(NT-proBNP)浓度检测及超声心动图检查,并取8周末及16周末处死大鼠的心肌组织行HE及Van Gieson(VG)染色,计算心肌胶原容积分数(CVF)。结果:与对照组比较,8周末模型组大鼠左室收缩末期内径(LVEDD),左室舒张末期内径(LVESD),NTproBNP均明显增大,左室射血分数(LVEF)及左室短轴缩短率(LVFS)均明显下降(均P<0.01),符合DCM的特征;与DCM组比较,LY294002组LVEDD,LVESD,NT-proBNP均减低,LVEF及LVFS均增高(P<0.05);组织病理学检查示:与对照组比较,模型组心肌间质明显纤维化且CVF明显增加(P<0.01),与DCM组比较,LY294002组心肌间质纤维化改善且CVF下降(P<0.01)。结论:LY294002可减轻DCM大鼠模型心肌纤维化,改善其心功能。

Objective： To examine the role of LY294002 in dilated cardiomyopathy （DCM） rats. cardiac function and myocardial structure in Methods： Fifty-two male SD rats were randomly assigned to a control group （n=16） and a DCM group （n=36）. The DCM rats were induced by intraperitoneal injection of adriamycin, and the control rats were given normal saline. After observation for 2 weeks, 6 rats from each group were killed randomly. In the end of the 8th week, the 24 DCM rats were randomly assigned to a DCM group （n=12） and a LY294002 group （n=12）, which were given normal saline and LY294002, respectively. In the end of the 8th week and 16th week, the cardiac function was analyzed by ultrasonic cardiogram （UCG） and the plasma was collected to test the level of N-terminal pro-brain natriuretic peptide （NT-pro BNP）. HE and Van Gieson （VG） staining were performed to calculate the collagen volume fraction （CVF）. Results： Compared with the control group, the left ventricular end-diastolic dimension （LVEDD）, left ventricular end-systolic dimension （LVESD） and NT-proBNP level of in the DCM rats were increased obviously, while the left ventricular ejection fraction （LVEF）, left ventricular fractional shortening （LVFS） in the DCM rats were decreased obviously （P〈0.01）. These changes were consistent with DCM characteristics. Compared with the DCM group, the LVEDD, LVESD and NT-proBNP levels in the LY294002 group were decreased, while the LVEF and LVFS were increased （P〈0.05）. Histopathology showed that the myocardium in the DCM rats was fibrotic and the CVF was increased compared with the control rats （P〈0.01）. The myocardial structure was improved in the LY294002 group compared to the DCM group. Conclusion： LY294002 can reduce the myocardial fibrosis in the DCM rats and improve the cardiac function.