瘦素受体突变对老年大鼠心肌的影响

Effects of leptin receptor gene mutation on myocardium in aged mice

目的探讨瘦素受体突变与心肌老化之间的关系。方法选择20月龄的瘦素受体基因突变老年大鼠（实验组）为对象，同月龄野生型CB57BL／6小鼠为对照组，观察瘦素受体基因突变对老年大鼠心肌老化（左心室射血分数、短轴缩短率、心肌超微结构和细胞凋亡及活性氧自由基水平）的影响。结果与对照组比较，实验组左心室射血分数下降42．8％（P〈0．01），短轴缩短率下降了48．8％（P〈0．01）；实验组心肌超微结构发生明显退变，而对照组鼠的心肌超微结构正常；与对照组比较，心肌细胞凋亡数量显著增加[分别为（2．53±0．37）个／200倍视野与（5．90±2．06）个／200倍视野，P〈0．05]；心肌胞内总活性氧自由基水平显著升高[分别为（2630．0±249．5）mfu与（3273．0±334．4）mfu，P〈0．053。结论瘦素受体突变，加快、加重了心肌老化，其机制可能与线粒体细胞凋亡、氧化应激有关。

Objective To investigate the effect of leptin receptor gene mutation on myocardium tissue in aged mice. Methods Both wild type control mice （WT） and leptin receptor mutant mice （Lepr^db ） at the age of 20 months were used in the experiments. Left ventricular function was detected by two dimension echocardiography, apoptosis in myocytes were measured by TUNEL assay, the uhrastructure of cardiomyocytes were observed by electron transmission microscope, and the level of intracellular total reactive oxygen species was determined by 2＇, 7 Ldichlorofluorescin （DCFH） assay. Results Compared with wild type controls, ejection fraction （EF）% and fractional shortening （FS）% of Lepr^db were decreased by 42.8% （P〈0.01） and 48.8% （P〈0.01）. Uhrastructure figures of cardiomyocytes kept normal in WT group while several abnormal morphologic alterations appeared in mitochondria and sarcoplasmic reticulum in Lepr^db group. TUNEL assay demonstrated the more apoptotic cardiomyocytes[（5.90±2.06）/200 field of vision] and the increased trend in reactive oxygen species（ROS） level（3273.0±334.4）mfu in Lepr^db heart, as compared with those in WT heart [（2.53±0.37）/200 field of vision, （2630.0±249.5）mfu, all P〈0.053. Conclusions Leptin receptor gene mutation results in the accelerated myocardium aging, the mechanisms may be the mitochondrion-associated events such as oxidative stress and apoptosis.