【摘要】 目的　观察β1受体反义寡核苷酸对肾性高血压大鼠降压和预防心室重塑的作用。方法　建立两肾一夹(2K1C)大鼠肾血管性高血压心肌肥厚模型术后 4 周随机分为 4 组:(1)β1 反义寡核苷酸组;(2)反向寡核苷酸组;(3)2K1C对照组;(4)假手术组。8周后行血流动力学分析,应用病理学方法评价整体心肌肥厚和组织胶原的表达。免疫组化方法检测 MMP- 2、TIMP- 2 的表达情况。结果　与假手术组相比,两肾一夹组大鼠术后发生明显左心室肥厚和纤维化,心率(HR)、收缩压(SBP)、左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室重量指数(LVWI)、胶原的含量及 MMP 2、TIMP- 2的表达显著高于健康的对照组,左室最大收缩和舒张速率(±dp/dtmax)均显著降低。β1 受体反义寡核苷酸能降低HR、SBP、LVSP、LVEDP、LVWI,而±dp/dtmax均显著升高;减少左室心肌中总体胶原中的合成及MMP -2、TIMP -2表达。结论　β1受体反义寡核苷酸改善血流动力学和左室功能;有效地防止心肌肥厚及细胞外重塑,这一效应与其降低心肌中高表达的MMP 2有关。更多还原

【Abstract】 Objective To study the effect of antisense oligoncucleotides (AS-ODN) of beta 1-adrenergic receptor on reduction of blood pressure and preventive vertricular remodeling in renovascular hypertensiverat. Metheds 2K1C-RHT rats were categorized into 4 groups:(1)AS-ODN group;(2)Inverse-ODN group;(3)2K1C group;(4)sham groups. Eight weeks later, the parameter of hemodynamics was determined. Cardiac hypertrophy and organization of collagen were evaluated by morphological examination. Protein expression of matrix metalloproteinase(MMP-2)and tissue inhibitor of metalloproteinase(TIMP-2)were examined by immunohistochemical analysis. Results Compared with sham operated group, left ventricle (LV) hypertrophy and fibrosis were predominantly occurred in 2K1C group after operation. HR, SBP, LVSP, LVEDP, LVWI, MMP-2,TIMP-2 were all significantly increased in 2K1C group. After AS-ODN of β\-1AR treatment, HR,SBP, LVSP, LVEDP, LVWI were decreased, while LV +dp/dt \{max\}, -dp/dt \{max\} were both increased. LV total collagen and the expression of MMP-2, TIMP-2 were decreased. ConclusionMMP-2, TIMP-2 are involved in the cardiac extracelluar matrix remodeling. Antisense oligoncucleotides of beta 1-adrenergic receptor improves hemodynamics and LV function and prevents the cardiac hypertrophy and extracellular matrix remodeling.更多还原