曲美他嗪对慢性心力衰竭大鼠的心肾保护作用及其机制探究

目的探讨曲美他嗪对慢性心力衰竭(CHF)大鼠的心肾保护作用及其机制。方法将24只雄性Wistar大鼠随机分为对照组、模型组和实验组各8只。采用肾上腹主动脉缩窄法建立CHF模型,给予实验组大鼠曲美他嗪10mg/(kg·d)灌胃,给予模型组和对照组大鼠等量的生理盐水灌胃。3组大鼠均灌胃4周。比较3组大鼠的左室舒张末压(LVEDP)、左心室压力最大上升速率(+dp/dtmax)、左心室压力最大下降速率(-dp/dtmax);比较3组大鼠心肌组织在HE染色、肾组织在Masson染色下结构的变化;比较3组大鼠肾功能指标血尿素氮(BUN)、肌酐(Scr);采用蛋白质印迹法(Western bloting),比较3组大鼠肾组织基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、α-平滑肌肌动蛋白(α-SMA)和转化生长因子-β(TGF-β)的蛋白表达。结果与模型组大鼠相比较,实验组大鼠的LVEDP明显降低,+dp/dtmax、-dp/dtmax明显升高(均P<0.05);BUN、Scr明显降低(均P<0.05);水肿比例明显减小,心肌纤维排列比较整齐,细胞肿胀程度明显减轻(P<0.05);肾组织胶原纤维面积/视野面积的比值明显减小,肾小球毛细血管处胶原纤维增生明显减少(P<0.05);MMP-2、MMP-9、α-SMA、TGF-β蛋白相对表达量明显降低(均P<0.05)。结论曲美他嗪可以明显保护CHF大鼠的心肾功能,能够改善心肾组织结构。

Protective effect of trimetazidine on heart and kidney of chronic heart failure rats and its mechanism

Objective To explore protective effect of trimetazidine on heart and kidney of chronic heart failure(CHF)rats and its mechanism.Methods 24male Wistar rats were randomly divided into control group,model group and experimental group,8cases in each group.CHF models were established by suprarenal abdominal aortic coarctation method.The rats in experimental group were administered with 10mg/(kg·d)trimetazidine.The rats in model group and control group were given same amount of normal saline.Three groups were intragastrically administered for 4 weeks.The left ventricular end-diastolic pressure(LVEDP),maximum increased rate of left ventricular pressure(+dp/dtmax)and maximum decreased rate of left ventricular pressure(-dp/dtmax)were compared among the three groups.The structure changes in myocardial tissues under HE staining and renal tissues under Masson staining were compared among the three groups.The renal function indexes such as blood urea nitrogen(BUN)and creatinine(Scr)were compared among the three groups.Western blotting was performed to compare protein expression of matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9),α-smooth muscle actin(α-SMA)and transforming growth factor-β(TGF-β)among the three groups.Results Compared with model group,LVEDP was significantly decreased in experimental group,while+dp/dtmax and-dp/dtmax were significantly increased(P<0.05).Compared with model group,BUN and Scr were significantly decreased in experimental group(P<0.05).Compared with model group,edema proportion was significantly reduced in experimental group,arrangement of myocardial fibers was neat,and cell swelling degree was significantly alleviated(P<0.05).Compared with model group,ratio of collagen fiber area/field area of renal tissue was significantly decreased in experimental group,and collagen fiber hyperplasia of glomerular capillaries was significantly decreased(P<0.05).Compared with model group,relative expression quantities of MMP-2,MMP-9,α-SMA and TGF-βprotein were significantly decreased in experimental group(P<0.05).Conclusion Trimetazidine can significantly protect heart and kidney function of CHF rats,and improve structure of heart and kidney tissues.