肝细胞生长因子联合缬沙坦对自发性高血压大鼠心肌细胞凋亡的影响

Effects of hepatocyte growth factor and valsartan on myocardial apoptosis in spontaneously hypertensive rats

目的观察肝细胞生长因子(HGF)联合缬沙坦对自发性高血压大鼠(SHR)心肌凋亡的影响。方法 24只14周龄雄性SHR随机分为4组(n=24):阳性对照组(P组,常规饲养,无药物干预)、HGF组(H组,开胸,左心室壁五点直接注射5×109Pfu/mL Ad5-HGF,0.1 mL,术后常规饲养4周),缬沙坦组(V组,缬沙坦灌胃30 mg·kg-1·d-1,4周),HGF联合缬沙坦组(HV组,开胸,左心室壁五点直接注射5×109Pfu/mL Ad5-HGF,0.1 mL,术后缬沙坦灌胃30 mg·kg-1·d-1,4周),雄性Wistar大鼠(WKY)为健康对照(N组,n=6)。治疗前及治疗后每周测量一次尾动脉压。4周后处死大鼠,TUNEL法测心肌凋亡指数,ELASA法测心肌HGF、caspase-3浓度,免疫组织化学法及图像分析系统分析心肌Bcl-xl水平。结果治疗4周后,HV组、V组血压较P组、H组明显下降(P<0.05);与P组相比,H组、V组、HV组心肌凋亡指数及心肌caspase-3浓度明显降低(P<0.05),心肌HGF、抗心肌凋亡蛋白Bcl-xl水平明显升高(P<0.05),且联合用药组尤为显著。结论HGF、缬沙坦均可有效抑制SHR左心室心肌细胞凋亡,改善心室重构,且联合使用效果优于HGF、缬沙坦的单独应用。

Objective To observe the effect of HGF combined with valsartan on myocardial apoptosis in spontaneously hypertensive rats.Methods 24 -old male SHRs age,14 -week,were randomly divided into 4 groups：positive control group （P group,conventional breeding,with no drug intervention）,HGF group （H group,the left ventricle walls were injected with 0.1ml 5×10^9Pfu/mL Ad5 -HGF at five different points after thoracotomy and then fed them normally for 4 weeks）,valsartan group （V group,intragastric administration of valsartan 30 mgokg-1od-1 for 4 weeks）,HGF plus valsartan group （HV group,the left ventricle walls were injected with 0.1ml 5x109Pfu/mL Ad5 -HGF,at five different points after thoracotomy and then valsartan at a dose f 30 mgokg-1od-1was intragastrically administrated for 4 weeks）,and male Wistar rats （WKY）were used as normal controls （N group,n=6）.The tail blood pressure was measured once a week before and after treatment.The rats were sacrificed at the 4th week.The myocardial apoptosis index was measured by TUNEL,and the concentration of myocardial HGF and caspase-3 was measured by ELASA,the level of myocardial Bcl-xl was analyzed by immunohistochemistry and image analysis system.Results After 4 weeks＇ treatment,blood pressure in HV group and V group significantly de-creased （P〈0.05）.Compared with P group,H group,V group and HV group showed significant decrease in myocardial apoptosis index and myocardial caspase-3 levels（P〈0.05 ）,while increase in myocardial HGF and anti myocardial apoptosis protein Bcl-xl levels （P〈0.05 ）.Compared with H group or V group,HV group showed better effect.（P〈0.05）.Conclusion The combination of HGF and valsartan have better effect on myocardial apoptosis of SHR ventricular than HGF or valsartan alone.