缬沙坦与硝苯地平对自发性高血压大鼠左心室肥厚心肌细胞G 蛋白偶联受体激酶2的表达及亚细胞分布的影响

Effects and Comparision of Valsartan and Nifedipine on the Expression and Subcellular Distribution of G Protein-coupled Receptor Kinase 2 in Left Ventricular Hypertrophy of Spontaneously Hypertensive Rats

目的 观察缬沙坦及硝苯地平对自发性高血压大鼠（SHR）左心室肥厚心肌细胞G 蛋白偶联受体激酶2（GRK2）的表达及亚细胞分布的影响.方法 选择自发性高血压大鼠（SHR）为研究对象（n=30）,随机分为对照组（n=6）,低剂量缬沙坦组[L 缬沙坦,10 mg /（kg·d）,n=6],高剂量缬沙坦组[H缬沙坦,30 mg /（kg·d）,n=6],低剂量硝苯地平组[L 硝苯地平,10 mg /kg,2 次/ d,n=6],高剂量硝苯地平组[H 硝苯地平,30mg /（kg·次）,2 次/d,n=6],由6 月龄喂养至8月龄,处死后分离心脏,通过免疫荧光标记、激光共聚焦显微镜及Werstern Blot 等方法,观察左心室心肌细胞GRK2的表达及亚细胞分布的变化.结果 与对照组比较,两药物干预的SHR 左心室心肌细胞膜蛋白GRK2表达及分布减少,高剂量较低剂量又有进一步减少,差异均有统计学意义（均P＜0.05）.缬沙坦组左心室心肌细胞膜蛋白GRK2表达及左心室重量较硝苯地平组减少,差异有统计学意义（P＜0.05）.相关性分析结果示两药物干预组大鼠左心室心肌细胞膜蛋白GRK2透光密度与左心室重量呈正相关（缬沙坦组r＝0.837,硝苯地平组r＝0.829,均P＜0.01）.结论 缬沙坦与硝苯地平改善左心室肥厚可能与抑制SHR 左心室心肌细胞膜蛋白GRK2表达有关,缬沙坦较硝苯地平能更好地改善心肌肥厚可能与其抑制GRK2表达使其进一步减少有关.

Objective To investigate the effects of valsartan and nifedipine on the expression and subcellular distribution of G protein-coupled receptor kinase 2 in left ventricular hypertrophy of SHR rats. Methods Using spontaneously hypertensive rats （SHR）（6-month-old） as the research object （n=30）,divided into control group （SHRC group）（n=6） ; low-dose valsartan group [L valsartan, 10mg/（ kg· d ）, 11.=6], high-dose valsartan group [H valsartan, 30mg/（ kg· d ）, n=6] ; Low-doses of nifedipine group [L nifedipine, 10mg/kg, bid, n=6], high-doses of nifedipine group [H nifedipine, 30mg/kg, bid,n=6] .Feeding to 8-month-old,put to death and dissect of the heart,using immunofluorescent labeling ,and laser confocal microscope and werstern blotting methods,observe the expression and subcellular distribution of GRK2 in left ventricular hypertrophy of SHR rats. Results （1） Confocal laser microscopy and Western blot results showed that： Compared with the control group ,the expression and distribution of GRK2 in left ventricular myocardial membrane protein reduced in the two drug.The high-dose group is much lower than the low-dose group.In Valsartan group, the expression of GRK2 in left ventricular membrane protein is lower than other groups. Compared with nifedipine group, the left ventricular mass further reduced（P〈0.05 ）. （2）Correlation analysis showedthat two medicine intervention group of left ventricular myocardial membrane protein GRK2 transmittance density was positively correlated with left ventricular mass（ Valsartan group r = 0.837;nifedipine group r = 0.829,all P〈0.01 ）. Conclusion Valsartan and nifedipine inhibit the improvement of left ventricular hypertrophy in SHR rats may be associated with left ventricular GRK2 expression of membrane proteins.Compared with nifedipine,the better inhibition of cardiac hypertrophy effects of valsartan may be related to the further reductionof the expression of GRK2.