Janus激酶转导和转录活化因子(Stat3)在Goldblatt鼠左室肥厚心肌中的变化以及缬沙坦干预后的变化

Change of the Janus Kinase-signal Transducer and Activator of Transcription 3 in the Left Hypertrophic Ventricle of Goldblatt rats as well as after Intervention of Valsartan

目的 观察Stat3在Goldblatt鼠左室肥厚心肌中的变化以及血管紧张素Ⅱ (AngⅡ ) 1型 (AT1)受体拮抗剂缬沙坦干预后Stat3活化与机械负荷、左室结构、局部AngⅡ含量的相互关系 ,探讨AT1-Stat3信号通路在左室肥厚发生发展中的作用。方法 采用两肾一夹法建立Goldblatt鼠模型 ,32只健康雄性SD大鼠随机分为高血压非治疗组 (H组 ,n =11) ,缬沙坦治疗组 (V组 ,n =11,术后两周开始缬沙坦 30mg/kg·d灌胃 ) ,假手术组 (C组 ,n =10 ) ,每周测 1次尾动脉压 ,每两周测 1次超声心动图 ,术后第 10周测定大鼠颈动脉压 ,处死大鼠 ,免疫组化检测左室心肌Stat3活化 ,放免检测左室心肌AngⅡ的含量。结果术后 10周H组颈动脉压 (SBP)、左室收缩末期经线室壁应力(MESS)、左室重量指数 (LVMI)、左室心肌Stat3的活化及AngⅡ的含量较C组均明显增高 (P <0 0 1) ,V组上述指标较H组显著下降 (P <0 0 1) ,与C组相比无著性差别 (P >0 0 5 )。Stat3活化与术后 10周SBP、MESS、LVMI、AngⅡ的含量呈正相关。 结论 Goldblatt鼠左室肥厚过程中Stat3活化增加 ,心肌局部AngⅡ以及持续的压力负荷对Stat3活化均起到重要的作用 ,活化的Stat3可能又促进AngⅡ的生成。缬沙坦通过与AT1受体结合在逆转左室肥厚的同时明显抑制Stat3活化并降低心肌?

Objective The aim is to investigate the role of the AT 1 -Stat3 pathway in the development of left ventricular hypertrophy(LVH) of hypertension. Methods The Goldblatt model of renovascular hypertension was induced in 22 male Sprague-Dawley rats which were randomizedto untreated hypertesion group (group H, n =11), valsartan treatment group(group V, n =11, 30 mg/kg·d). Ten nonoperated SD rats were served as control group (group C, n =10). The tail cuff blood pressure was detected every week and echocardiogram was detected every other week. After 10 weeks of operation the rats were sacrificed and left ventricles were collected. Immunohistochemistry was used to examine the activation of Stat3. Left ventricular concentration of Ang Ⅱ was assessed by radioimmunoassay.Results After ten weeks of operation, the blood pressure, meridional end systolic stress (MESS) and LV mass index(LVMI) were elevated in group H than in group C. After 8 weeks treatment of valsartan, BP, MESS, and LVMI in group V were lower significantly than those of group H. Activation of Stat3 and concentration of Ang Ⅱ in left ventricle were greater in group H than that in group C and group V. The activation of Stat3 positively correlated with the SBP, MESS, LVMI and concentration of Ang Ⅱ in the left ventricle. ConclusionIn the development of LVH, Ang Ⅱ in LV and sustained pressure overload may induce Stat3 activation. Furthermore activated Stat3 might feedback and contribute to the production of local Ang Ⅱ. Valsartan inhibit the activation of Stat3, reduce the concentration of Ang Ⅱ in left ventricle and reverse the progression of LVH, suggessting AT 1 -Stat3 is probably a pathway in the signal transduction of left ventricular hypertrophy.