不同鼠龄的人多巴胺D5^F173L突变基因转基因高血压小鼠血压及心脏结构与功能分析

Analysis of the Blood Pressure and Cardiac Structure and Function in Human Dopamine D5^(F173L) Transgenic Mice at Different Ages

目的通过对不同年龄多巴胺D5F173L突变基因及D5正常基因转基因小鼠的血压和心脏结构与功能进行分析,了解多巴胺D5受体在高血压发生发展过程中的作用。方法利用无创血压测量仪和高分辨率小动物超声系统检测两种转基因小鼠的血压和左心室壁厚度、左心室内径、左心室容积、射血分数、短轴缩短率和左心室质量等心脏功能指标。结果 D5F173L转基因小鼠4月龄、6月龄、16月龄时收缩压、舒张压都明显高于D5转基因小鼠;4月龄、6月龄的D5F173L转基因小鼠与D5转基因小鼠相比舒张期和收缩期左室壁厚度均明显增大、左室内容积均明显变小、左心室重量增加;16月龄的D5F173L转基因小鼠与D5转基因小鼠相比左心室前壁增厚、心腔内径缩短,心腔容积下降、心室重量增加、射血分数提高、短轴缩短率提高;在18月龄时D5F173L转基因小鼠相比于D5转基因小鼠左心室收缩期前壁厚度增加,后壁厚度减少,舒张期前壁厚度增加,后壁厚度减少;另外在18月龄时D5F173L转基因小鼠与其16月龄时相比,射血分数、短轴缩短率明显降低,收缩期左心室容积明显增大。结论 D5F173L转基因小鼠的血压及心脏功能与结构的分析结果符合原发性高血压的特征。D5F173L转基因小鼠可作为原发性高血压动物模型。

Objective To analyze the role of D5^F173L mutation in the development of hypertension,and to detect the blood pressure,cardiac structure and function changes in the D5^F173L mutation gene and the D5 gene transgenic mice at different ages.Methods The blood pressure was detected with an intelligent non-invasive blood pressure measuring instrument（SoftronTM）.The cardiac structure and function were examined with a high-resolution small animal ultrasound system（Sonics Vevo770）.Results Both systolic and diastolic blood pressures of the D5^F173L transgenic mice were significantly higher than that in the 4-month,6-month and 16-month old D5 transgenic mice.Compared with the 4-month and 6-month old D5 transgenic mice,the ventricular wall thickness and ventricular mass of the D5^F173L transgenic mice wasincreased,while the left ventricular volume decreased.Compared with the D5 transgenic mice at the age of 16 months,the left ventricular wall thickness,cardiac chamber diameter shortening and cardiac chamber volume in the D5^F173L transgenic mice were decreased,while the ventricular weight,ejection fraction and fractional shortening rate were increased.The D5F173L transgenic mice showed an obvious remodeling compared to 18-month old D5 transgenic mice,with a decease of the left ventricular systolic anterior wall and posterior wall,and increase of the diastolic wall.Conclusion The changes of blood pressure,cardiac function and cardiac remodeling of the D5F173L transgenic mice show a similar phenotype with that of human primary hypertension.The D5^F173L transgenic mouse can be used as a primary hypertension animal model.