三甲氧苄嗪对低流量灌流大鼠心肌细胞葡萄糖转运蛋白-1、4mRNA表达的影响  

Effect of Trimetazidine and Low Flow Ischemia on the Expression of GLUT - 1 and GLUT - 4 mRNA in the Isolated Perfused Rat Heart

作　　者：周国鹏[1] 赵志杰[1] 祁芸芸[1] 

机构地区：[1]北京大学第一医院老年科,北京100034

出　　处：《中国医药导刊》2001年第5期380-382,384,共4页Chinese Journal of Medicinal Guide

摘　　要：目的:通过离体心脏灌注模型,观察低流量缺血及TMZ对大鼠心肌细胞葡萄糖转运蛋白-1、4(glucose transportertypel、4,GLUT1/4)mRNA表达的影响。方法:成年、雄性Wistar大鼠,分为:(1)对照组(N);(2)缺血再灌注组(R);(3)缺血组(I);(4)预处理/缺血(PI);(5)预处理/缺血/再灌注组(PR)。另取12只雄性Wistar大鼠,喂以TMZ14日,随机分为TMZ对照组(TC)和TMZ缺血/再灌注组(TR)。各组均测定灌流液LDH、CK含量,并用RT-PCR方法观察心肌GLUT-1/GLUT-4mRNA表达的变化。结果:预处理和TMZ饲喂明显降低心肌缺血及再灌注期间LDH和CK的释放;GLUT-1mRNA含量:I组、B组、PI组、PR组、TC组和TR组明显高于正常对照组(P值均小于0.05);R组、PI组和PR组含量明显低于I组(P值均小于0.05);PR组和R组或PI组间比较,差值没有显著意义;TR组GLUT-1mRNA含量明显高于R组及PR组(P值均小于0.05);而TR组和I组比较则无显著差异。各组间GLUT-4mRNA含量变异大,没有显著差异。结论:低流量缺血显著增加了心肌GLUT-1mRNA的表达,而对GLUT-4mRNA的含量没有显著的影响;而再灌注后,GLUT-1mRNA含量较再灌注开始前有所下降,但仍高于基础状态。口服TMZ增加非缺血心肌在正常氧供状态下GLUT-1mRNA表达,有助于提高心脏对低流量缺血的耐受性。Objective: Myocardial ischemia increases heart glucose utilization in vivo. But whether oral TMZ could alter the level of mRNA expression of GLUT - 1 and GLUT - 4 is not fully investigated. Method: 30 adult, male Wistar rats were assigned random-lyinto:(1)normal(N) ; (2)ischemia/reperfusion(R) ; (3)ischemia(I) ; (4)preconditioning/ischemia(PI) ;(5)preconditioning/ischemi-a/reperfusion(PR) . An additional 12 rats were fed with trimetazidine (TMZ) for 2 weeks, and assigned into group TMZ control (TC) and TMZ ischemia/reperfusion (TR) . LDH and Ck leakage during ischemia and reperfusion were assessed. And the mRNA expressions of GLUT - 1 and GLUT - 4 in rat myocytes were measured using RT - PCR method with internal standard. Result: preconditioning and oral TMZ significantly reduce the LDH and CK release during reperfusion. For GLUT - 1 mRNA contents, those of group I, R, PI, PR, TC and TR were significantly higher than that of group N . And in group R, PI and PR, they are lower than group I. No difference was found between group Pr, Pi and R . The mRNA expression of GLUT - 1 significantly in group TR compared with group R and PR. No difference was found among the GLUT - 4 mRNA expressions of those groups. Conclusion: low flow ischemia significantly increased the GLUT - 1 mRNA expression, but had little effect on the mRNA content of GLUT - 4. After reperfusion, the GLUT - 1 mRNA content decreased slightly, but still above basal level. Oral TMZ can increase the GLUT - 1 mRNA content of myocytes under normoxia conditions, and thus would help the heart less susceptible to ischemia/reperfusion injuries.

关 键 词：心肌缺血 葡萄糖转运蛋白 三甲氧苄嗪 心肌保护 动物实验 

分 类 号：R541[医药卫生—心血管疾病]