别嘌呤醇在心力衰竭大鼠能量代谢中的保护作用

Allopurinol preserves myocardial energy metabolism in chronic heart failure rats

目的:研究别嘌呤醇allopurinol(ALLO)对心力衰竭(心衰)大鼠能量代谢的影响及其可能机制。方法:6周龄的雄性SD大鼠35只,随机分为对照组(13只)、ALLO处理组(12只)和假手术组(10只),建模后第2天,ALLO处理组给予ALLO灌胃,对照组和假手术组给予0.9%氯化钠灌胃。8周后,检测大鼠心功能,左心室非梗死区黄嘌呤氧化酶(xanthine oxidase,XO)、过氧化物酶体增殖活化受体γ共激活因子-1α(peroxidase body proliferation activated receptor gamma activation factor 1alpha,PGC-1a)、肉毒碱棕榈酰转移酶1(carnitine palmitoyltransferase 1,CPT-1)、葡萄糖转运蛋白4(glucose transporter,GLUT4)mRNA和蛋白表达水平,心肌组织形态学变化和心肌细胞超微结构。结果:对照组与假手术组相比,建模组大鼠心功能明显降低(P<0.05),PGC-1α、CPT-1mRNA和蛋白表达水平明显降低(P<0.05),XO、GLUT4mRNA和蛋白表达明显升高(P<0.05),HE染色显示心肌组织排列紊乱、细胞水肿,电镜显示肌丝大量溶解,线粒体肿胀空泡化。与对照组相比,ALLO处理组心功能明显改善(P<0.05),PGC-1α、CPT-1mRNA和蛋白表达水平升高(P<0.05),XO、GLUT4mRNA和蛋白表达水平下降(P<0.05),HE染色显示心肌结构排列较整齐、细胞水肿减轻。电镜显示肌丝溶解和线粒体肿胀减轻。结论:ALLO改善心衰大鼠心肌细胞能量代谢,可能与通过PGC-1α轴来调节糖脂代谢,进而增加ATP的生成有关。

Objective：To explore the mechanism of allopurinol（ALLO）in improving cardiac function via myocardial energy metabolism in rats with heart failure.Method：The 35 male SD rats（6-weeks old）were randomly arranged into the ALLO Group（n=12）,the Control Group（n=13）and the Sham-Operated Group（n=10）.Two days after surgery,all of the animals were treated with administration by gavage as the above protocol.Eight weeks later,cardiac function of the animals were estimated by echocardiography in vivo,and the expressions of XO,PGC-1a,CPT-1,GLUT4 in non-infarction area,the myocardial morphological changes and ultrastructure changes of myocardial cells were detected in vitro.Result：Compared with the rats in sham-operated group,those in model groups were demonstrated poor cardiac function by echocardiography（P〈0.05）,the PGC-1αand CPT-1expression decreased significantly（P〈0.05）,the XO and GLUT4 expression increased significantly（P〈0.05）.Tissue morphology analysis showed loose and edematous tissue by HE staining in the model groups than that in the sham-operated group,and it was also observed lysis of myofilament,swollen and bubbled mitochondria under electron microscopy in the model groups than that in the sham-operated group.While compared with control group,rats in ALLO treatment group were demonstrated better cardiac function by echocardiography（P〈0.05）,the PGC-1αand CPT-1expression increased（P〈0.05）,the XO and GLUT4 expression decreased significantly（P〈0.05）,loose and swollen tissue was alleviated,lysis of myofilament and swollen mitochondria was also alleviated.Conclusion：ALLO could improve myocardial energy metabolism in rats with chronic heart failure,it maybe connected with the fact that ALLO modulated PGC-1αin glucolipid metabolism and enhanced the generation of ATP.