Plin5促进心肌脂肪储积减轻心脏脂毒性损伤  

Plin5 alleviates myocardial lipotoxic injury by promoting intracellular lipid storage

作　　者：武杰[1] 王超[2] 郑鹏飞[3] 袁媛[1] 徐明[4] 叶菁[1] 

机构地区：[1]第四军医大学基础部病理学与病理生理学教研室,陕西西安710032 [2]第四军医大学唐都医院检验科,陕西西安710032 [3]第四军医大学西京医院心脏内科,陕西西安710032 [4]第四军医大学基础部生理学教研室,陕西西安710032

出　　处：《心脏杂志》2015年第5期514-519,共6页Chinese Heart Journal

基　　金：国家自然科学基金课题项目资助(31171132;30700263);陕西省自然科学基础研究计划项目资助(2013JQ4020)

摘　　要：目的观察脂滴表面蛋白(Plin)5对小鼠心脏形态、功能及其脂质代谢的影响,探讨可能的作用机制。方法对成年Plin5基因敲除小鼠进行心脏超声分析、心脏组织油红染色、心肌组织中三酰甘油(TAG)和游离脂肪酸(FFA)含量检测、心肌细胞超微结构透射电镜观察、心肌组织与细胞中丙二醛(MDA)的含量和超氧化物歧化酶(SOD)活性检测等。结果与同窝野生型小鼠相比,Plin5基因敲除成年小鼠心脏肥厚、心肌细胞肥大,并伴有心脏收缩功能下降和射血功能明显降低,同时其心脏组织中脂滴的含量明显降低,MDA的含量增加,SOD的活性显著下降。Plin5基因的缺失可显著增加油酸处理的心肌细胞氧化应激的水平。结论 Plin5可通过影响心脏组织中脂滴的含量,调节心肌细胞脂肪酸氧化和脂质过氧化水平,其表达缺失可导致心脏中活性氧簇(ROS)产物大量聚集,引发过氧化应激损伤,最终导致心肌的肥厚和心脏功能降低。AIM To explore the role of Plin5, a lipid droplet-binding protein involved in the metabolism of lipid droplets in cardiac lipid metabolism in mice by a Plin5 knockout mouse model in vivo and in vitro. METHODS： Adult Plin5 ＋/＋ and Plin5-/- mice were randomly assigned to wild-type and knockout groups. Echocardiography was recorded for the indexes of left ventricular internal diameter at end-diastole （LVIDd）, left ventricular internal diameter at end-systole （LVIDs） , left ventricular anterior wall thick- ness at end-systole （LVWTs） and left ventricular ejection fraction （LVEF）. Heart weight and body weight were recorded after sacrifice and heart weight to body weight ratio （HW/BW） was calculated. H/E and Oil Red O staining were used to observe the morphologic changes and cardiac lipid contents, and electron microscopy was used to analyze the changes of mitoehondria and lipid droplets. Triacylglycerol （TAG） , free fatty acids （FFA） , malondialdehyde （MDA） and superoxide dismutase （SOD） contents were also measured and analyzed. RESULTS Plin5-deficient mice exhibited reduced cardiac lipid droplet accumulation with hypertrophied heart and reduced cardiac functions. Plin5 deficiency induced significant oxidative burden in the heart as evidenced by increased MDA content and decreased SOD activity in Plin5 knockout mice hearts and Plin5-/- cardiomyocytes treated with oleic acid. CONCLUSION Plin5 deficiency increases myocardial fatty acid oxidation and oxidative burden, thereby inducing cardiac hypertrophy and cardiac dysfunction.

关 键 词：脂滴表面蛋白5 心肌肥大 脂肪酸氧化 氧化应激 小鼠 

分 类 号：R542.2[医药卫生—心血管疾病]