缬沙坦对自发性高血压大鼠心肌细胞凋亡的影响

目的探讨遗传性高血压及心肌肥厚过程中心肌细胞凋亡的意义及AT1受体拮抗剂缬沙坦对其的影响. 方法　实验动物为8周龄自发性高血压大鼠（SHR）,分为缬沙坦治疗组（SHR+缬沙坦组）和非治疗组（SHR无药组）,以Wistar鼠作为正常血压对照,观察期限为8-16周.采用TUNEL染色法检测心肌组织凋亡细胞数. 结果　缬沙坦治疗后血压降至163±6?mm?Hg,与治疗前175±3?mm?Hg及无药组193±7?mm?Hg比较显著降低.SHR+缬沙坦组心脏指数3.22±0.19?mg/g,较SHR无药组4.02±0.31?mg/g显著降低.SHR+缬沙坦组与SHR无药组比较,前者TUNEL阳性细胞数显著减少至接近Wistar组. 结论　心肌细胞凋亡是代偿性心肌肥厚发展为心力衰竭的可能机制之一.高血压病早期缬沙坦在降压同时有效抑制心肌细胞凋亡.

Influence of Valsartan on myocardial apoptosis in spontaneously hypertensive rats

Objective To explore the pathogenic changes of myocardial apoptosis in heart hypertrophy during hypertension and evaluate the anti-apoptosis effect of Valsartan. Methods Thirty spontaneously hypertensive rats (SHRs) were divided into two groups: 15 treated with Valsartan (20?mg*kg-1*d-1) (SHR+Valsartan group), the others with placebo (SHR+placebo group), with 15 normal Wistar rats as control. Systolic blood pressure was measured by the tail-cuff method. The observation period was from 8 to 16 weeks of age. Cardiac apoptosis was evaluated by a Terminal Deoxynucleotidyl Transferase-Mediated dUTP-biotin Nick End Labeling (TUNEL) assay. Results Mean blood pressure values were 127±2?mm?Hg in controls, 163±6?mm?Hg in the SHR+Valsartan group and 193±7?mm?Hg in the SHR+placebo group at 16 weeks of age, whereas the blood pressure in 8-week-old SHR and Wistar rats were 175±3?mm?Hg and 125±5?mm?Hg, respectively. The ratio of the heart weight over body weight declined in Wistar (3.07±0.03?mg/g) and SHR+Valsartan groups (3.22±0.19?mg/g) compared with the SHR+placebo group (4.02±0.31?mg/g) (P<0.05). The density of TUNEL-positive cells in Wistar and SHR±Valsartan groups was 23.3±3.3 nuclei/HPF and 35.0±1.3 nuclei/HPF, both of which were significantly less than that of the SHR+placebo group (116.7±11.3 nuclei/HPF). Conclusions In response to chronic pressure overload, cardiomyocyte-specific apoptosis contributes to the transition from compensatory hypertrophy to decompensation. Apoptosis may be effectively inhibited by Valsartan in the early stage of hypertension.