扎考比利改善压力超负荷致大鼠心室重构的作用  

Zacopride attenuates pressure overload-induced ventricular remodeling in rats

作　　者：刘成芳[1] 任芳芳 和荣丽[1] 张卫国[1] 皇甫平[1] 吴博威[2] LIU Cheng-fang;REN Fang-fang;HE Rong-li;ZHANG Wei-guo;HUANG-FU Ping;WU Bo-wei(Department of Human Anatomy,Shanxi Medical University,Taiyuan 030001,China;Department of Physiology,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学人体解剖学教研室,山西太原030001 [2]山西医科大学生理学教研室,山西太原030001

出　　处：《中国病理生理杂志》2019年第2期206-211,共6页Chinese Journal of Pathophysiology

基　　金：山西省自然科学基金资助项目(No.2015021177);山西医科大学博士启动基金资助项目(No.03201405);山西医科大学大学生创新基金资助项目(No.20172214)

摘　　要：目的:研究扎考比利(zacopride,ZAC)对腹主动脉缩窄所致大鼠压力超负荷性心室重构的改善作用。方法:通过腹主动脉缩窄构建大鼠压力超负荷心室重构模型,预防性给予ZAC、氯喹(chloroquine,Chlor)及ZAC+Chlor。连续给药8周,超声心动图评价心功能;计算心重/体重比(HW/BW)和左心室/体重比(LVW/BW);左心室心肌组织HE染色;透射电镜观察心肌细胞超微结构;Western blot检测大鼠心肌组织内向整流钾通道(IK1)蛋白表达;RT-PCR法检测心肌组织Kir2.1的mRNA表达。结果:与模型(vehicle)组相比,ZAC组大鼠心功能明显改善,LVEDS和LVEDD明显降低(P <0.05),LVEF和LVFS显著升高(P <0.01),HW/BW和LVW/BW显著降低(P <0.05),心肌肥大程度降低,心肌细胞横断面积明显减小(P <0.01),心肌超微结构明显改善。Chlor明显阻断了ZAC对腹主动脉缩窄所致压力超负荷大鼠心室重构的保护作用。与vehicle组相比,ZAC组大鼠心肌组织IK1蛋白表达和Kir2.1的mRNA显著升高(P <0.01)。结论:心肌IK1激动剂ZAC显著减轻大鼠左心室压力超负荷诱发的心室重构。AIM:To investigate the protective effect of zacopride(ZAC)on the pressure-overload left ventricular remodeling in the rats induced by coarctation of abdominal aorta.METHODS:Male Sprague-Dawley(SD)rats with pressure overload were induced by the coarctation of abdominal aorta.The model rats were intraperitoneally administered with ZAC,chloroquine(Chlor),and zacopride+chlorquine(ZAC+Chlor).The study duration was 8 weeks.The cardiac structure and function were assessed by echocardiography.The heart weight/body weight(HW/BW)ratio and the left ventricular weight/body weight(LVW/BW)ratio were calculated.The changes of structure and shape in myocardial tissue were observed with HE staining.The ultrastructure of the myocytes was observed under transmission electron microscope.The inward rectifier potassium channel(IK1)protein expression was determined by Western blot.The mRNA expression of Kir2.1 was detected by RT-PCR.RESULTS:Compared with vehicle group,ZAC improved cardiac function,as indicated by the decreased left ventricular end-diastolic dimension(LVEDD)and left ventricular end systolic dimension(LVESD)(P<0.05),and the increased left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(P<0.01).The HW/BW and LVW/BW ratios were significantly decreased,and the cross-sectional area of the cardiomyocytes was significantly less in ZAC group than that in vehicle group(P<0.01).The ultrastructure of the myocytes was significantly improved.Chlor blocked the protective effect of zacopride on the pressure-overload left ventricular remodeling.The protein level ofmRNA expression of Kir2.1 in the cardiac tissues in ZAC group were significantly increased compared with vehicle group(P<0.01).CONCLUSION:ZAC significantly attenuates pressure overload-induced ventricular remodeling in rats.

关 键 词：扎考比利 压力超负荷 心室重构 内向整流钾通道 

分 类 号：R541.6[医药卫生—心血管疾病] R363.2[医药卫生—内科学]