高游离脂肪酸血症对心肌结构与功能的影响及其机制  

The Effect and Pathophysiological Mechanism of High Free Fatty Acids(FFAs)on the Cardiac Structure and Function

作　　者：柯柳[1] 余叶蓉[1] 张玄娥[1] 张祥迅[1] 陆志明[1] 

机构地区：[1]四川大学华西医院内分泌科,成都610041

出　　处：《四川大学学报（医学版）》2009年第1期24-28,共5页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(批准号30570874)资助

摘　　要：目的观察在肥胖/胰岛素抵抗状态下高游离脂肪酸(FFA)血症与心肌结构及功能的关系,并探讨其可能的分子发病机制。方法4周龄雄性SD大鼠16只,随机分为2组,肥胖组(OB组)予高脂饲料喂养,对照组(NC组)予正常饲料喂养。行高胰岛素-正糖钳夹实验评价大鼠外周胰岛素敏感性,检测左心室最大收缩速率(+dp/dtmax)、左心室最大舒张速率(-dp/dtmax)及平均心肌细胞直径(MCD)。检测血及左室心肌匀浆甘油三酯(TG)、胆固醇(TC)、游离脂肪酸(FFA)和血管紧张素Ⅱ(AngⅡ)水平以及心肌核转录因子κB(NF-κB)、I-κB、诱生型一氧化氮合酶(iNOS)的表达。结果OB组存在明显胰岛素抵抗(P<0.05),MCD较NC组增大(P<0.01),心脏舒、缩功能均下降(P<0.01),血及心肌TG、FFA、AngⅡ浓度均较NC组升高(P<0.05),心肌iNOS、NF-κB表达增强(P<0.01)、I-κB表达下降(P<0.01)。心肌TG与血FFA呈正相关(r=0.80,P<0.01),心肌FFA与心肌AngⅡ水平(r=0.74,P<0.05)、iNOS(r=0.66,P<0.05)及NF-κB表达(r=0.86,P<0.01)呈正相关。+dp/dtmax与心肌TG(r=-0.87,P<0.01)、AngⅡ(r=-0.52,P<0.05)、iNOS(r=-0.70,P<0.01)及NF-κB表达(r=-0.57,P<0.01)均呈负相关。-dp/dtmax与心肌TG(r=-0.85,P<0.01)、AngⅡ(r=-0.82,P<0.01)、iNOS(r=-0.78,P<0.01)及NF-κB表达(r=-0.75,P<0.01)均呈负相关。结论肥胖-胰岛素抵抗大鼠由于血中TG、FFA浓度升高,导致心肌异位脂质沉积。异位沉积的脂质有可能通过激活心肌RAS系统,并增强心肌NF-κB、iNOS的表达,从而引起心肌肥大、心肌细胞凋亡、心功能损害的发生。Objective To study the pathophysiological links between elevated circulating FFAs concentration and the cardiac structure, and their function in obese insulin resistance rat model. Methods 4 weeks age male SD rats were fed with high-fat chow （OB） or standard laboratory chow （NC） respectively. Whole-body insulin sensitivity, the maximum velocity of myocardial contraction （＋dp/dtmax） and the maximum velocity of myocardial diastole （-dp/dtmax） of intracardiac pressure, and myocardiac cell diameter （MCD） were measured. The concentrations of triglyceride （TG）, FFAs and angiotensin Ⅱ （Ang Ⅱ ） both in blood and in left ventricular portions of heart and the expressions of NF-κB,I-κB and iNOS in myocardium were analyzed. Results OB group developed obesity and left ventricular hypertrophy, and their insulin sensitivity was much lower than that of control group. Obese rats had higher plasma concentrations of TG, FFAs and Ang Ⅱ. Accordingly, dramatic lipid deposition occurred within cardiomyocytes of obese rats, and the value of myocardiac Ang Ⅱ was also increased. High-fat diet also induced a progressive decrease in values of ＋dp/dtmax and -dp/dtmax. The higher expressions of NF-κB and iNOS in myocardium were observed in OB group, while IκB lower. Intramyocardial lipid deposition was associated with plasma FFAs concentrations （r=0.80, P〈0.01）. Intramyocardial FFAs concentration was associated with myocardial Ang Ⅱ concentration （r=0.74, P〈0.05）and changes in expressions of NF-κB （r=0.86, P〈0.01）, iNOS （r=0.66, P d0.05）. The contractile dysfunction was associated with intramyoeardial lipid deposition （r= -0.87, P〈0.01）, Ang Ⅱ （r=-0. 52, P〈0.05） and expressions of NF-κB （r=-0.57, P〈0.01）, iNOS （r=-0. 70, P〈0.01）. The diastolic dysfunction was associated with intramyocardial lipid deposition （r= -0.85, P〈0.01）, Ang Ⅱ （r=-0.82, P〈0.01） and expressions of NF-κB （r= -0.75, P〈0. 01）, iNOS （r= -0.78, P〈0.01）. C

关 键 词：胰岛素抵抗 游离脂肪酸 异位脂质沉积 心功能受损 

分 类 号：R589.2[医药卫生—内分泌]