Research Of Antisense Oligoncucleotides Of Beta₁-adrenergic Receptor On Left Ventricular Remodeling In Renovascular Hypertensive Rats

Backgroud Hypertension is a chornic of multifactorial and multigenetic disease, persistent high biood pressure leads to left vertricular hypertrophy(LVH), LVH is frequent clinical with significant morbidity and mortality comprising an independent cardiac risk factor;hemodynamics and neurohormone are importment cause of LVH elements, one of sympathetic nervous system be activated is chief regulate and compensation mechanis. β-adrenergic receptor is important function in the process of vertricular remodeling and apoptosis. Matrix metalloproteinases(MMPs) are a family of endoproteinases containing Zn²+.which is specificity degradation extracellular matrix.MMPs are present in the myocardium and are capable of degradation all the matrix components of the heart, which are significant promote degradation extracellular matrix in the vertricular remodeling. Furthermore, increase in MMP express and activity be relevant to vertricular remodeling; concern delay and prevent vertricular remodeling development research which is hot spot in the cardioangiology realm.Object To observe the effect of Antisense oligoncucleotides of beta₁-adrenergic receptor reduction on blood pressure and preventive vertricular remodeling in renovascular hypertensive ratMetheds Models of renovascular hypertensive ( 2KIc -RHR) were made. 2KIc- RHR rats categorized into 5 groups: (1) AS-ODN group; (2) IN-ODNgroup; (3) 2KIc group; (4) sham groups; (5)Carvedilol group. Eight weeks later,the parameter of hemodynamics was determined, cardiac hypertrophy and organizetion of collagen were evaluated by morphologica examination. protein expression of matrix metalloproteinase (MMP-2), tissue inhibitor of metalloproteinase ( TIMP-2 ) was examined by immunohistochemical analysis.Results Comparaed with sham operated group, induced left ventricle ( LV) hypertrophy and fibrosis predominantly occurred 2KIc group after operation. HR, SBP . LVSP> LVEDP. LVM, LVMI, MMP-2, TIMP-2 all significant increased in 2KIc group; A significant decrease could seen in -dp/dtmax and +dp/dtmax. After antisense gene treatment, In comparsion with 2klc group, Antisense oligoncucleotides of betai-adrenergic receptor decrease could be seen in HR, SBP. LVSP, LVEDP, LVMI, While significant increase could be seen in+dp/dtmax, -dp/dtmax;LV total collagen and the expression of MMP-2, TIMP-2 were decreased.Conclusion MMP-2, TIMP-2 are involved in the cardiac extracelluar matrix remodeling . Antisense oligoncucleotides of betai-adrenergic receptor can improve hemodynamics and LV function, prevent the cardiac hypertrophy and extracelluar matrix remodeling, which is associated with the attenuation of myocardial MMP-2.