卡维地洛与压力负荷心衰大鼠心室重塑和Rho激酶表达的关系

目的研究卡维地洛(α1肾上腺素受体阻断剂、β肾上腺素受体非选择性阻断剂)对升主动脉缩窄压力超负荷心力衰竭大鼠心室重塑、RhoA、Rho激酶表达的影响,探讨卡维地洛改善心力衰竭的新机制。方法将升主动脉缩窄术后心力衰竭Wistar雌性大鼠随机分为2组,一组为心力衰竭组,给予生理盐水灌胃,每日2次(n=10);一组为卡维地洛组,12.5mg/Kg卡维地洛灌胃,每日2次(n=10),治疗12周。同时制备模型设置假手术组作为对照(n=10),不予处置。观察各组大鼠各项指标变化。结果与假手术组相比,心力衰竭大鼠心肌肥厚指数增加,HE染色心肌排列紊乱,血液动力学指标明显异常,心肌细胞RhoA、Rho激酶表达显著升高(P<0.05);药物治疗12w后,与心力衰竭组对比,卡维地洛治疗组心肌肥厚指数降低,HE染色示心肌重塑不明显,血液动力学参数改善,RhoA、Rho激酶表达显著降低。结论卡维地洛可通过对心肌细胞α-Gq-RhoA/Rho激酶通路表达干预,明显缓解心力衰竭症状、改善心室重塑,卡维地洛这种α1肾上腺素受体阻断剂可能对心力衰竭更有利。

Relationship of Carvedilol with Cardiac Remodeling and the Expression of Rho Kinase in Pressure Overload Induced Heart Failure Rats

Objective To study the effect of dalitrend （α 1, and β-adrenoreceptor inhibitor） on cardiac remodeling, RhoA and Rho kinase gene expression in heart failure pressure overload rat models subsequent to coarctation of ascending aorta and to elucidate the effects and new mechanism of dilatrend on heart failure. Method A model of heart failure induced by coarctation of ascending aorta was used in this study. 20 female Wistar heart failure rats were divided randomly into two groups （n=10）： heart failure （Natrii chloridi） and dilatrend （12.5mg/Kg, Bid po for 12 weeks after coarctation of ascending aorta operation）, 10 age-matched sham operation group as control. Hemodynamics, ratio of LV weight to body weight, HE dyeing, expression of RhoA and Rho kinase were investigated. Result Hemodynamics paremeters were unnormal, the ratio of left ventricular weight to body weight（left ventricular hypertrophic index） was increased, expression levels of RhoA and Rho kinase mRNA in cardiac muscles were significant higher in heart failure when compared with sham operation group （P 〈 0.05）. However, hemodynamics paremeters were similar to normal, the ratio of left ventricular weight to body weight（left ventricular hypertrophic index） was decreased, expresion levels of RhoA and Rho kinase mRNA in cardiac muscles were significant lower in dilatreml treatment than in heart failure（P 〈 0.05）. Conclusion Dalitrend may contribute to the beneficial effects on heart failure and cardiac remodeling by downregulation of RhoA and Rho kinase mRNA expression, α1-Gq-RhoA/Rho kinase signaling pathway may be one of the mechanisms of dalitreud treating heart failure and ventrieular remodeling.