摘要
目的:研究短链酰基辅酶A脱氢酶(short-chain acyl-coenzyme A dehydrogenase,SCAD)重组腺病毒(SCAD recombinant adenovirus,Ad-SCAD)对自发性高血压大鼠(spontaneously hypertensive rats,SHR)心肌肥厚和纤维化的影响。方法:以12周龄SHR为心肌肥厚和纤维化模型,以Wistar大鼠为正常对照,尾静脉注射Ad-SCAD治疗8周。将大鼠为Wistar+Ad-GFP组、SHR+Ad-GFP组、Wistar+Ad-SCAD组和SHR+Ad-SCAD组。观察各组大鼠血压、左室重量指数、超声心动图数据和心脏形态学变化;检测左心室羟脯氨酸含量、SCAD蛋白和mRNA表达、心肌肥厚和纤维化标志物的mRNA表达、SCAD酶活性、ATP含量及游离脂肪酸含量的变化。结果:与Wistar+AdGFP组相比,SHR+Ad-GFP组出现明显的病理性心肌肥厚和纤维化。与SHR+Ad-GFP组相比,SHR+Ad-SCAD组SCAD蛋白和mRNA表达水平及酶活性均显著升高,左心室前、后壁肥厚显著减轻,左心室内径显著增大,心脏舒张功能改善,心肌肥厚显著减轻,胶原沉积明显减少,心肌纤维化明显减轻,心肌组织的ATP含量明显升高,游离脂肪酸含量显著降低。结论:尾静脉注射Ad-SCAD能显著减轻SHR心肌肥厚和纤维化。
AIM:To investigate the effects of over-expression of short-chain acyl-coenzyme A dehydrogenase(SCAD)on myocardial hypertrophy and fibrosis in spontaneously hypertensive rats(SHR).METHODS:The SHR were regarded as myocardial hypertrophy and fibrosis model,while Wistar rats served as normal controls.The SCAD recombi-nant adenovirus(Ad-SCAD)was injected into the tail vein for 8 weeks.The animals were divided into Wistar+Ad-GFP group,SHR+Ad-GFP group,Wistar+Ad-SCAD group and SHR+Ad-SCAD group.The systolic blood pressure,left ven-tricular mass index and echocardiographic data of the rats in each group were statistically analyzed,and the morphological changes of cardiac tissues were observed.The changes of hydroxyproline content,SCAD enzyme activity,SCAD protein and mRNA levels,mRNA levels of myocardial hypertrophy and fibrosis markers,ATP content,and free fatty acid content were determined.RESULTS:Compared with Wistar+Ad-GFP group,significant myocardial hypertrophy and fibrosis were observed in SHR+Ad-GFP group.Compared with SHR+Ad-GFP group,the protein and mRNA levels and enzyme ac-tivity of SCAD were significantly increased,left ventricular wall hypertrophy decreased significantly,left ventricular diam-eter increased significantly,cardiac diastolic function was significantly improved,myocardial hypertrophy was alleviated,collagen deposition was significantly reduced,and myocardial fibrosis was significantly attenuated in SHR+Ad-SCAD group.Furthermore,ATP content was significantly increased and free fatty acid content was significantly decreased in SHR+Ad-SCAD group.CONCLUSION:Intravenous injection of Ad-SCAD significantly attenuates cardiac hypertrophy and fibrosis in SHR.
作者
冯静韵
廖英勤
钟小艺
苏永少
马智超
秦学
潘雪刁
刘培庆
路静
周四桂
FENG Jing-yun;LIAO Ying-qin;ZHONG Xiao-yi;SU Yong-shao;MA Zhi-chao;QIN Xue;PAN Xue-diao;LIU Pei-qing;LU Jing;ZHOU Si-gui(Department of Clinical Pharmacy,School of Pharmaceutical Sciences,Guangdong Pharmaceutical University,Guangzhou 510006,China;Department of Pharmacology and Toxicology,School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2021年第5期809-817,共9页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81670239)
广东省自然科学基金资助项目(No.2020A1515010223)
广东省“十二五”医学重点学科建设项目(No.2012-20)。
关键词
短链酰基辅酶A脱氢酶
自发性高血压大鼠
心肌肥厚
心肌纤维化
脂肪酸β氧化
Short-chain acyl-coenzyme A dehydrogenase
Spontaneously hypertensive rats
Cardiac hypertrophy
Myocardial fibrosis
Fatty acidβ-oxidation
