福辛普利对自发性高血压左心室肥厚大鼠心肌细胞凋亡的影响

目的：探明福辛普利对伴左心室肥厚（LVH）的自发性高血压大鼠（SHR）心肌细胞凋亡的影响。方法：采用末端脱氧核糖核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）技术检测SHR和WKY大鼠左心室心肌细胞凋亡变化。另外，将12只10月龄SHR随机分为两组，分别给予生理盐水（Control组）和福辛普利(Fosinopril组）腹腔内注射进行为期8周的干预治疗，以探明福辛普利对SHR的LVH和心肌细胞凋亡的影响。结果：（1）SHR组LVH指数显著高于WKY大鼠组（P＜0．01）；（2）SHR组凋亡阳性心肌细胞核数目和心肌细胞凋亡指数均显著低于WKY大鼠组（P＜0．01）；（3）SHR组心肌细胞凋亡指数与LVH指数呈显著负相关（P＜0．01）。（4)Fosinopril组LVH指数较Control组显著降低，但凋亡阳性心肌细胞核数目和心肌细胞凋亡指数较Control组显著增加（P均＜0．01）。结论：（1）SHR左心室心肌细胞凋亡不足可能在LVH发病中起重要作用。（2）Fosinopril 能显著改善SHR的LVH，其 机制之一可能与促进心肌细胞凋亡有关。

Effect of Fosinopril on cardiomyocyte apoptosis in spontaneously hypertensive rats with left ventricular hypertrophy

Objective To explore the effect of Fosinopril on cardiomyocyte apoptosis in spontaneously hypertensive rats'(SHRs')with left ventricular hypertrophy.Methods 6 SHR aged 10 months were used as SHR group while 6 age and sex-matched Wistar Kyoto rats(SKY)as normal control group(WKY group).Apoptotic cardiomyocyte nuclei in the left ventricle from SHR and WKY were quantified using in situ TdT-mediated dUTP nick end labeling(TUNEL)technique.In addition,12 SHR at 10 months of age were randomly divded into 2 groups according to age, sex and body weight-matched, and treated for 8 weeks intraperitoneal injection with Fosinopril (Fosinopril group) and normal saline(Control group) respectively.The treatment effect of above drugs on left ventricular hypertrophy and cardiomyocyte apoptosis was also observed.Results (1)Left ventricular hypertrophic index(left ventricle weight/body weight,LVW/BW)was higher in SHR group than that in WKY group(P value less than 0.01);(2)Apoptotic cardiomyocyte nuclei and apoptotic index(calculated by dividing the number of apoptotic cardiomyocyte nuclei by the total number of cardiomyocyte nuclei and multiplying that value by 100) were lower in SHR group than those in WKY group(all P value less than 0.01);(3)Apoptotic index in the left ventricle was inversely correlated with left ventricular hypertrophic index(LVW/BW) in SHR(n=6,r=-0.90,P<0.01,y=3.24--0.09x);(4)Left ventricular hypertrophic index (LVW/BW)was significantly decreased,but apoptotic cardiomyocyte nuclei and apoptotic index increased markedly in Fosinopril group compared with control group(all P value less than 0.01 ).Conclusions (1)The decreasing of cardiomyocyte apoptosis in left ventricle may play an important role in the occurrence of LVH in SHR;(2)Fosinopril can singificantly improve LVH of SHR,the mechanism of its modifying LVH of SHR may be related to increasing of cardiomyocyte apoptosis triggered by it.