【摘要】 目的:研究腺相关病毒（adeno-associated virus,AAV）介导的微小RNA-124（miR-124）过表达对野百合碱（monocrotaline,MCT）诱导的肺动脉高压（pulmonary arterial hypertension,PAH）大鼠右心重构的作用。方法:32只健康雄性SD大鼠随机分为4组:正常对照（control）组、MCT+生理盐水（normal saline, NS）组、MCT+AAV-GFP （MCT+GFP）组和MCT+AAV-miR-124 （MCT+miR-124）组。后3组大鼠麻醉后经气管导管分别缓慢注入100μL NS、AAV-GFP和AAV-miR-124,3周后经腹腔注射MCT（60 mg/kg）建立PAH模型。测量大鼠右心室收缩压（RVSP）和平均动脉压,计算右心室肥厚指数（RVHI）和右心室重量指数（RVWI）。右心组织病理切片行天狼星红染色,观察心肌的病理改变。RT-qPCR检测miR-124在肺和右心组织中的表达水平。Western blot检测右心组织中转化生长因子β₁（TGF-β₁）和p-Smad2的表达水平。结果:与control组相比,MCT+NS和MCT+GFP组大鼠的RVSP、RVHI、RVWI、TGF-β₁表达和p-Smad2表达均显著增加（P<0.05）,右心室心肌细胞显著肥大,胶原沉积显著增多;与MCT+GFP组相比,MCT+miR-124组RVSP、RVHI、RVWI、TGF-β₁表达和p-Smad2表达均显著降低（P<0.05）,右心室心肌细胞肥大程度显著减轻,胶原沉积显著减少。结论:过表达miR-124可有效降低MCT诱导的大鼠RVSP,减轻右心重构,其机制可能与下调TGF-β₁和p-Smad2的表达有关。更多还原

【Abstract】 AIM: To investigate the effect of microRNA-124（miR-124） over-expression mediated by adeno-associated virus（AAV） on right ventricular remodeling in rats with pulmonary arterial hypertension（PAH） induced by monocrotaline（MCT）. METHODS: Male SD rats（n=32） were randomly divided into 4 groups: normal control（control） group, MCT+normal saline（NS） group, MCT+AAV-GFP（MCT+GFP） group and MCT+AAV-miR-124（MCT+miR-124） group. The rats in the latter 3 groups were instilled slowly with 100 μL NS, AAV-GFP and AAV-miR-124 by orotracheal instillation after anesthesia, respectively. Three weeks later, MCT（60 mg/kg） was intraperitoneally injected to establish the PAH model. Right ventricular systolic blood pressure（RVSP） and mean arterial pressure of the rats were measured, and right ventricular hypertrophy index（RVHI） and right ventricular weight index（RVWI） were calculated. The pathological sections of the right heart were stained with Sirius red, and the pathological changes of myocardium were observed under a microscope. The expression of miR-124 in the lung tissues was detected by RT-qPCR. The protein levels of transforming growth factor-β₁（TGF-β₁） and p-Smad2 in right heart tissues were determined by Western blot. RESULTS: Compared with control group, RVSP, RVHI, RVWI and the protein levels of TGF-β₁ and p-Smad2 in MCT+NS group and MCT+GFP group were significantly increased（P<0.05）, the right ventricular myocytes were significantly enlarged, and collagen deposition was significantly increased. However, compared with MCT+GFP group, RVSP, RVHI, RVWI and the protein levels of TGF-β₁ and p-Smad2 in MCT+miR-124 group were significantly decreased（P<0.05）, the degree of right ventricular myocyte hypertrophy was significantly reduced, and collagen deposition was significantly reduced. CONCLUSION: Over-expression of miR-124 obviously reduces RVSP of rats induced by MCT and relieves myocardial remodeling, which may be related to the down-regulation of TGF-β₁ and p-Smad2.更多还原