肥胖大鼠血脂和体脂肪变化及心室肌细胞内钙离子强度与心律失常发生的关系

The level of serum lipids, body-fat content of obesity rats, and the relationship between intracellalar calcium and ventricular arrhythmia

目的观察高脂饮食诱导肥胖（DIO）大鼠血脂和体脂肪变化，探讨心室肌细胞内钙离子强度与心律失常发生的关系。方法健康雄性SD大鼠60只，体质量200～250g。将大鼠按体质量随机分为对照组（15只）和高脂饮食组（45只），高脂饮食组采用高脂饮食诱导法建立肥胖大鼠模型。喂养12周后，在高脂饮食组筛选体质量增加明显的大鼠进入肥胖组（15只）。两组各选8只大鼠舌下注射0．1mg／kgBaCl2，诱导心律失常，应用标准Ⅱ导联心电图连续监测1h，评价大鼠心律失常发生率及严重程度。采集两组大鼠腹主动脉血，分离血清，测血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇。分离大鼠肾周脂肪、睾周脂肪和肠系膜脂肪，称重、计算体脂比。酶解法分离大鼠单个心室肌细胞，应用激光共聚焦技术记录细胞内钙离子强度（[Ca^2＋]i）。结果肥胖组大鼠体脂比[（7．71±0．74）％]明显高于对照组[（4．69±0．37）％]，两组比较差异有统计学意义（t=3．650，P〈0．05）；血清总胆固醇、甘油三酯和低密度脂蛋白水平，肥胖组[（1．26±0．04）、（0．58±0．10）、（0.51±0．04）mmol／L]与对照组[（0．92±0．08）、（0．29±0．03）、（0．31±0．04）mmo]／L]比较显著增高（z值分别为3．801、2．778、3．536，P〈0．05）；肥胖组大鼠心律失常发生率高于对照组（χ^2=5．333，P〈0．05），心律失常评分肥胖组（2．5±0．6）高于对照组（0）；肥胖组大鼠心室肌细胞内钙离子强度（247．96±20．03）明显高于对照组（174．25±23．13），两组比较差异有统计学意义（t=2．409，P〈0．05）。结论肥胖大鼠心律失常发生率增加，血脂升高，心肌细胞内钙离子积聚是引发肥胖源性心律失常的主要机制之一。

Objective To study the level of serum lipids and body-fat content of high-fat diet induced obesity rats（DIO）, explore the relationship between intraccllular calcium and ventrieular arrhythmia. Methods Sixty male Sprague-Dawley （SD） rats were divided into control group （15） and experiment group （45）, high-fat diet was administrated for 12 weeks to established obesity model, 15 rats were selected into obesity group according to their body weight gain. The standard 2-lead electrocardiograph was used to detect the incidence and scores of arrhythmia induced by barium chloride （BaCI2, 0.1 mg/kg） for 1 hour on every 8 rats from different groups respectively. Body-fat content, the level of serum total cholesterol （TC）, triglyceride （TG）, low density lipoprotein cholesterol （LDL-C） and high density lipoprotein cholesterol （HDL-C） were measured. The epididymal （EP）, retroperitoneal （RE） and mesenteric （ME） white adipose pads was measured to obtain the body fat content. Single ventricular myocytes of rats were isolated by enzymatic dissociation. The confocal laser scanning microscope was used to record basic intracellular calcium level（[Ca2＋]i）. Results The body-fat content in obesity group[ （7.71 ±0.74）%] was significantly higher than control group [ （4.69±0.37）%] （t = 3.650, P 〈 0.05）. The level of serum TC, TG and LDL-C were significantly higher（t = 3.801,2.778,3.536, P 〈 0.05） in obesity group[ （1.26± 0.04）, （0.58 ±0.10）, （0.51 ± 0.04）mmol/L] than those in control group[ （0.92±0.08）, （0.29± 0.03）, （0.31 ± 0.04） mmol/L]. The level of serum HDL-C was decreased gradually from control group[ （0.53±0.05）mmol/L] to obesity group [ （0.52 ± 0.02） mmol/L], but there was no significant difference between them （t = 0.186, P 〉 0.05 ）. The incidence of arrhythmia induced by BaCl2（0.1 mg/kg） in obesity group was significantly higher than control group（χ^2 = 5.333, P 〈 0.05）, and the scores of arrhythmia was increased in obesity group（2.5 ±0.6） too. The fluorescence intensity standing for[Ca^2＋]i was increased significantly （t = 2.409, P 〈 0.05） from obesity group （247.96 ± 20.03） to control group（174.25 ± 23.13）. Conclusion As the free cytosolic calcium begin to accumulate, the arrhythmia morbidity is increased in obesity rats.