老年高血压大鼠心肌细胞apelin—APJ系统的变化

Changes of apelin-APJ system in cardiomyocytes of rats with senile hypertension

目的探讨体外培养48h后的老年高血压大鼠心肌细胞apelin—APJ系统的变化。方法雄性sD大鼠16只，采用两肾一夹方法制备老年高血压大鼠模型（老年高血压组，n=8），以假手术组作为对照组（n=8）。术后20个月，心脏超声和血流动力学测定心功能和心室结构，检测血浆及心肌细胞培养48h后上清中apelin含量（ELISA法），心肌细胞APJ蛋白水平（Western印迹法）及环磷酸腺苷（cAMP）蛋白水平（ELISA法）。结果与对照组比，老年高血压组mSP（平均收缩压）、mDP（平均舒张压）、PP（平均脉压差）、LVDP（左室舒张末期压）、IVSd（舒张期室间隔厚度）、LVIDd（左心室舒张末期内径）、LVPWd（左心室舒张末期后壁厚度）显著升高（P〈0．05）；体质量、＋dp／dt（左室内压上升／下降最大速率）、FS％（左心室短轴缩短率）、EF％（左室射血分数）明显降低（P〈0．05）。大鼠左室心肌细胞培养48h后，老年高血压组培养上清中apelin分泌显著高于对照组[（0．80±0．12）μg／L比（0．41±0．08）μg／L，P〈O．05]；血浆apelin含量、心肌细胞APJ及cAMP蛋白表达显著低于对照组（P〈0．05）。结论长期高血压造成老年大鼠心室重构，其中cAMP作为apelin．APJ系统的第二信使参与了心室重构的发生发展。

Objective To determine the variation of apelin-APJ system in cardiomyocytes derived from rats with senile hypertension at 48 h following incubation in vitro. Methods Sixteen male SD rats were randomly allocated to be subjected to unilateral renal artery occlusion for establishment of senile hypertension model （senile hypertension group, n=8） or sham surgery （sham operation group, n=8） , respectively. At month 20 postoperatively, the cardiac function and ventricular remodeling were measured by eehocardiography and hemodynamic assay. The level of apelin in the plasma and myoeardiocyte supernatant was assayed at 48 h following incubation by using enzyme-linked immunosorbent assay （ELISA）. Western blotting was employed to examine the level of APJ protein, and ELISA was applied to determine the contents of cAMP protein. Results Compared with sham operation group, the senile hypertension group yielded significantly augmented levels of mean systolic blood pressure （mSP） , mean diastolic blood pressure （mDP） , difference of pulse blood pressure （PP） , left ventrieular end-diastolic pressure （LVDP） , interventricular septal diastolic thickness （IVSd）, left ventricular end-diastolic internal diameter （LVIDd） and left ventricular posterior wall thickness （LVPWd） （all P〈0.05） yet markedly reduced body weight, maximal left ventricular internal pressure increase/reduction velocity （±dp/dt） , left ventricular short axis reduction rate （FS%） and ejection fraction （EF%） （all P〈O.05）. In senile hypertension group, a marked increase in the secretion of apelin [ （0.80±0.12） μg/L vs （0.41 ±0.08） μg/L, P〈O.05] yet substantially a marked decrease in expression of plasma apelin, cardiomyocyte APJ and cAMP at 48 h following incubation were noted （all P〈0.05）. Conclusion The cAMP and apelin-APJ system acts as the second messengers inthe pathogenesis of ventricular remodeling as a consequence of prolonged hypertension.