基于呼吸代谢系统动态监测慢性心衰(心阳虚证)大鼠模型的建立及评价

The Dynamic Monitoring on the Establishment and Evaluation of Rat Model of Chronic Heart Failure with Heart Yang Deficiency Based on Respiratory Metabolism System

目的参考心阳虚慢性心衰的临床表现,通过前期结扎冠状动脉左前降支,后期给予一氧化氮合酶抑制剂(左旋硝基精氨酸)建立大鼠慢性心衰(心阳虚证)模型并给予评价。方法 Wistar大鼠按体质量随机分为假手术组、心阳虚慢性心衰模型组。冠脉结扎术后4周后,给予左旋硝基精氨酸(LNNA)4周致心衰发展模型,假手术组穿线不结扎。实验过程中采用无创的呼吸代谢系统动态监测大鼠的呼吸代谢、能量代谢变化情况作为模型评价的依据;最后采用血流动力学检测大鼠的心功能并及时记录造模过程中大鼠的死亡情况,外观体征、精神状况、饮食、排泄及水肿等状况。结果心阳虚慢性心衰模型组与假手术组比较,除第2周呼吸代谢及能量代谢较冠脉结扎初始增强明显外,第6周到第8周呼吸代谢及能量代谢明显减弱(P<0.01);模型组大鼠心率(HR)、左室舒张末期压(LVEDP)、左心室舒张所用时间(Tau)呈上升趋势(P<0.05);左室内压变化最大速率(±dp/dtmax)均呈降低趋势(P<0.01)。结论前期结扎冠状动脉左前降支,后期给予一氧化氮合酶抑制剂(左旋硝基精氨酸),通过采用呼吸代谢系统可以动态监测模型动物的状态和生理机能情况,可准确判断出模型出现的时间窗,从而为慢性心衰(心阳虚证)模型建立提供一种客观、无创的判断方法。

Objective： To establish and evaluate rat model of chronic heart failure with heart yang deficiency, according to the clinical manifestations of chronic heart failure,with the early ligation of the left anterior descend- ing coronary artery,and the latter nitric oxide synthase inhibitor （L-NNA）. Methods： Wistar rats were randomly divided into two groups ： the sham group and the model group of chronic heart failure with heart yang deficiency. Chronic heart failure was caused by coronary artery ligation in model group, the sham group threading without fig- ation. LNNA was given for 4 weeks to cause heart failure. Respiratory metabolism system was used to monitor the changes of respiratory metabolism and energy metabolism in rats during the experiment. The hemodynamics was used to evaluate the cardiac function of rats in each experimental group. At the end of the experiment, these data were recorded-Timely records of the deaths ,the appearance of signs, Mental status （such as behavior, movements breathing） diet, excretion and edema etc. Results： Different from the sham group, in the second week ,respiratory metabolism and energy metabolism were significantly enhanced, compared with the initial coronary artery ligation, while in the Sixth to eighth week,the respiratory metabolism and energy metabolism of time showed a gradual weakening trend （P 〈 0.01）. Conclusion： Early ligation of the left anterior descending coronary artery,and the later nitric oxide synthase inhibitor （L-NNA） to establish and evaluate rat model of chronic heart failuie with heart yang deficiency,with respiratory metabolism system can dynamically monitor the status and physiological function of animal,and accurately determine the time window of the model,providing an objective,noninvasive method to judge the rat model of chronic heart failure with heart yang deficiency.