曲美他嗪对糖尿病性心肌病大鼠心肌损伤保护作用研究

摘要

目的：探讨曲美他嗪对糖尿病性心肌病大鼠心肌损伤的保护作用机制。方法将健康雄性Wistar大鼠60只随机分为对照组、模型组、实验A组、实验B组、实验C组，每组12只。对照组采用标准颗粒饲料喂养；模型组和实验各组采用高糖高脂饲料喂养，于第6周一次性腹腔注射链脲佐菌素（FTZ ）30 mg／kg，注射后72 h，筛选血糖水平连续2次高于11．1 mmol／L的大鼠，继续原饲料喂养6周，同时实验A组、B组、C组分别腹腔注射10，30，90 mg／（ kg· d）曲美他嗪干预6周。末次给药12 h后，观察比较5组大鼠的心功能、心肌酶谱、TGF－β1蛋白及TGF－β1 mRNA表达情况。结果模型组的肌酸激酶（ CK ）、乳酸脱氢酶（LDH）、TGF－β1、丙二醛（MDA）、TGF－β1 mRNA水平均显著高于对照组和实验各组（P均＜0.05），超氧化物歧化酶（SOD）、miR－21水平显著低于实验各组和对照组（P均＜0．05）；实验各组CK、LDH、TGF－β1、MDA、TGF－β1 mRNA水平随着曲美他嗪用量的增加而逐步下降，SOD、miR－21水平则显著升高，实验C组的CK、LDH、TGF－β1、MDA、SOD、TGF－β1 mRNA、miR－21水平与对照组最接近，但CK、LDH、MDA、TGF－β1 mRNA水平仍高于对照组（P均＜0．05）。模型组FS、LVEF、IRVT、E／A均显著低于实验各组和对照组（P均＜0．05）；实验各组的E／A、FS、LVEF、IRVT均低于对照组（P均＜0．05），且随着曲美他用量的增加上述各指标逐步接近对照组。结论曲美他嗪可以通过调控MAPK－microRNA通路改善心肌酶、心功能等指标，保护心肌，减轻心室重构，随着剂量增加效果更加显著。%Objective It is to investigate the mechanism of the protective effect of trimetazidine on myocardial injury in the rats with diabetic cardiomyopathy .Methods 60 healthy male Wistar rats were selected and randomly divided into control group, model group, the experimental group A, experimental group B, experimental group C, each group had 12 rats.The control group was fed with standard pelleted diet , model group and every experimental group with high sugar and fat feed , all the rats were given streptozotocin (FTZ 30 mg/kg) by intraperitoneal injection on the sixth week , 72 h after injection, the rats whose blood glucose levels were higher than that of 11 .1 mmol/L for two times were selected and continue to feed with the o-riginal diet for 6 weeks, at the same time the experimental group A , B, C were treated with trimetazidine of 10, 30 and 90 mg/kg/d by intraperitoneal injection for 6 weeks.In 12 h after the last therapy, heart function, myocardial enzyme spectrum, TGF-β1 protein and the expression of mRNA of TGF -β1 of the rats in the five groups were observed and compared .Results The levels of CK , LDH, TGF-β1 , MDA, TGF-β1 mRNA in model group were significantly higher while the levels of SOD and miR-21 were lower than that of control group and experiment groups (P<0.05).The levels of CK, LDH, TGF-β1, MDA, TGF-β1 mRNA gradually decreased while the levels of SOD and miR -21 increased with the increasing of trimetazi-dine dose.The levels of CK, LDH, TGF-β1, MDA, SOD, TGF-β1 mRNA, miR-21 in group C were most closely to the control group, but the levels of LDH, MDA, TGF-β1 mRNA were still higher than that of control group (P<0.05).FS, LVEF, IRVT, E/A in model group were significantly lower than that of control group and experiment groups (P<005), FS, LVEF, IRVT, E/A in experiment groups were significantly lower than that of control group (P<005), and with the increase of trimetazidine dose these indices gradually close to the control group .Conclusion Trimetazidine can improve cardiac function and myocardiac enzymes , protect myocardium , reduce ventricular remodeling ,through regulation of MAPK -microRNA path-way, the effects were more significant with the increase of dosage .