CAJ | 학술논문

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5×109 Pfu/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5×109 Pfu/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。
목적：관찰간세포생장인자（HGF）연합힐사탄대자발성고혈압대서（SHR）심기조망적영향。방법24지14주령웅성SHR수궤분위4조（n＝24）：양성대조조（P조，상규사양，무약물간예）、HGF조（H조，개흉，좌심실벽오점직접주사5×109 Pfu/mL Ad5-HGF，0．1 mL，술후상규사양4주），힐사탄조（V조，힐사탄관위30 mg·kg-1·d-1，4주），HGF 연합힐사탄조（HV 조，개흉，좌심실벽오점직접주사5×109 Pfu/mL Ad5-HGF，0．1 mL，술후힐사탄관위30 mg·kg-1·d-1，4주），웅성Wistar대서（WKY）위건강대조（N조，n＝6）。치료전급치료후매주측량일차미동맥압。4주후처사대서，TUNEL법측심기조망지수，ELASA법측심기HGF、caspase-3농도，면역조직화학법급도상분석계통분석심기Bcl-xl 수평。결과치료4주후，HV조、V조혈압교P조、H조명현하강（P＜0．05）；여P조상비，H조、V조、HV조심기조망지수급심기caspase-3농도명현강저（P＜0．05），심기HGF、항심기조망단백Bcl-xl수평명현승고（P＜0．05），차연합용약조우위현저。결론 HGF、힐사탄균가유효억제SHR좌심실심기세포조망，개선심실중구，차연합사용효과우우HGF、힐사탄적단독응용。
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 5x109Pfu/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 im-age 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 myocar-dial apoptosis index and myocardial caspase-3 levels(P<0.05 ),while increase in myocardial HGF and anti myo-cardial 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.