实验性充血性心力衰竭AVP系统和AQP_2的变化及黄芪的作用

Study on Vasopressin Sydtem and Aquaporin-2 in Experimental Congestive Heart Faliure and Effects of Astragalus Membranaceus

目的 利用腹主动脉 下腔静脉瘘所致的慢性充血性心衰大鼠 ,研究心衰时心钠潴留的机制 ,观察精氨酸血管加压素 (AVP)和其V1a、V2 受体与AVP依赖性水通道水孔蛋白 2 (AQP2 )在其中的作用 ,以及黄芪对此的影响。方法 对腹主动脉 下腔静脉瘘所致的心衰大鼠在造瘘后的第一天起给予腹腔注射黄芪 0 .5g/ (kg·d) ,观察 5周后大鼠的心功能、肾功能指标的变化 ,并分别以斑点杂交与以GAPDH相对定量的RT PCR方法检测下丘脑AVP、主动脉与肾脏AVPV1a受体、肾脏AVPV2 受体与AQP2 mRNA的表达。结果 动静脉造瘘心衰大鼠心、肾功能较之假手术对照组明显下降 ,表现为右心房压力 (RAP)、左室舒张末压 (LVEDP)增高、左室 +dP/dtmax、GFR、RPF、尿量、尿钠排泄量与自由水清除率降低 ,黄芪可显著改善上述异常。斑点杂交检测表明下丘脑AVPmRNA表达在心衰大鼠上调 ;半定量RT PCR检测显示心衰大鼠主动脉与肾皮质AVPV1a受体mRNA表达减弱 ,在肾髓质表达增强 ;肾皮质V2 受体与AQP2 mRNA表达增强 ,髓质减弱。黄芪可明显改善心衰大鼠的心、肾功能指标 ,并能完全或部分纠正这些基因的异常表达。结论 在腹主动脉 下腔静脉造瘘所致的充血性心力衰竭大鼠中存在有AVP系统和AQP2 表达的异常 。

Purpose To investigate the role of vasopression (AVP) and its receptors as well as vasopressin dependent water channel AQP 2 in rats with aortocaval fistula (ACF) caused congestive heart failure.The effects of Chinese herb astragalus membranaceus (AM) were also observed. Methods AM was given intraperitoneally at a dose of 0.5 g/(kg·d) since the next day of ACF model preparation.Parameters for cardiac and renal functions were measured.Hypothalamic AVP mRNA expression was determined by dot blot analysis.Aortic and renal expressions of AVP V 1a mRNA and renal V 2 receptor and AQP 2 mRNA expressions were semi quantitated by RT?PCR. Results Rats with aortocaval fistula presented impaired acrdiac and renal functions as increased right atrial pressure (RAP)and left ventricular end diastolic pressure (LVEDP), dec reased+dP/dt max of the left ventricle,glomerular filtration rate (GFR),renal plasma flow (RPF),urine flow,urinary sodium excretion rate and free water clearance.AM could significantly improve these deteriorated functions.Dot blot analysis showed up regulated AVP mRNA expressions in the hypothalamus of the rat with fistula.AVP V 1a receptor mRNA expression was decreased in the aorta and renal cortex, while increased in renal medulla.The mRNA levels of V 2 receptor and AQP 2 were higher in the renal cortex while lower in the medulla in heart failure rats compared with those in the sham operated control.AM could correct or partially correct these abnormalities. Results Rats with aortocaval fistula presented impaired acrdiac and renal functions as increased right atrial pressure (RAP)and left ventricular end diastolic pressure (LVEDP), dec reased+dP/dt max of the left ventricle,glomerular filtration rate (GFR),renal plasma flow (RPF),urine flow,urinary sodium excretion rate and free water clearance.AM could significantly improve these deteriorated functions.Dot blot analysis showed up regulated AVP mRNA expressions in the hypothalamus of the rat with fistula.AVP V 1a receptor mRNA expression was decreased in the aorta and renal cortex, while increased in renal medulla.The mRNA levels of V 2 receptor and AQP 2 were higher in the renal cortex while lower in the medulla in heart failure rats compared with those in the sham operated control.AM could correct or partially correct these abnormalities. Conclusions Abnormal expressions of AVP system and AQP 2 exist in aortocaval fistula caused heart failure rats.Chinese herb astragalus membranaceus could exert beneficial influences on sodium water metabolism under this pathophysiological situation,which is partially mediated by its effects on AVP,AVP receptors and AQP 2.