参附注射液通过血管加压素逃避改善心衰大鼠水钠代谢  

Shenfu Injection Improves Water and Sodium Metabolism in Rats with Heart Failure by Vasopressin Escape

作　　者：梁昊[1] 黄建华 简维雄[1] 张稳[3] 胡思远 胡志希[1] 杨梦 Liang Hao;Huang Jianhua;Jian Weixiong;Zhang Wen;Hu Siyuan;Hu Zhixi;Yang Meng(Institute of TCM Diagnostics,Hunan University of Chinese Medicine,Changsha 410208;Institute of Herbs,Hunan Academy of Chinese Medicine,Changsha 410006;Department of Geriatrics,the First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007;School of Sports and Arts,Hunan University of Chinese Medicine,Changsha 410208)

机构地区：[1]湖南中医药大学中医诊断研究所,长沙410208 [2]湖南省中医药研究院中药研究所,长沙410006 [3]湖南中医药大学第一附属医院老年病科,长沙410007 [4]湖南中医药大学体育艺术学院,长沙410208

出　　处：《中药药理与临床》2020年第6期57-62,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(编号:81503627、81774208、81973753);湖南省教育厅科研项目(编号:18K070);湖南省保健专项资金项目(编号:B2015-07);湖南省中医药管理局科研项目(编号:2015092)。

摘　　要：目的:通过参附注射液作用于异丙肾上腺素诱导的心衰大鼠模型以证实其是否可通过血管加压素(AVP)逃避改善心衰后的水液代谢。方法:除空白对照组外,其余大鼠用异丙肾上腺素制作心衰模型,监测大鼠尿量、体重,随后将成模大鼠随机分为:模型对照组、参附10 ml/kg组、螺内酯20 mg/kg组、参附20 ml/kg+螺内酯20 mg/kg组、参附10 ml/kg+螺内酯20 mg/kg组、参附5 ml/kg+螺内酯20 mg/kg组。大鼠处死前,从主动脉采血,检测大鼠血管加压素(AVP)和N-末端脑钠肽前体(NT-proBNP)水平;通过荧光定量PCR和Western Blot对大鼠肾髓质水通路蛋白-2(AQP-2)、血管加压素受体-2(V_(2)R)的mRNA和蛋白表达进行检测。结果:造模时,与空白对照组相比,造模大鼠体重增多,尿量减少(P<0.05),血清AVP、NT-proBNP含量明显升高,V_(2)R mRNA上调,蛋白下调,AQP-2蛋白上调(P<0.05或P<0.01)。用药后,与模型对照组相比,螺内酯20 mg/kg组和参附20 ml/kg+螺内酯20 mg/kg组、参附10 ml/kg+螺内酯20 mg/kg组、参附5 ml/kg+螺内酯20 mg/kg组的尿量均明显升高(P<0.05);各组AVP含量明显降低(P<0.05);V_(2)R mRNA、NT-proBNP含量、AQP-2、V_(2)R蛋白表达明显下调(P<0.05)。与3个联合组相比,其他各组AQP-2、V_(2)R蛋白表达均明显上调(P<0.05)。结论:参附注射液能够改善心衰大鼠的水钠潴留,与降低AVP及其受体V_(2)R的表达有关,这是对水钠潴留作用的逃避机制;但参附注射液的利尿作用有限,可能不及螺内酯,需要与传统利尿剂合用才能产生强大的利尿效果。Objective:To study the influence of Shenfu Injection on isoproterenol induced heart failure to confirm its effect of escaping from vasopressin(AVP)to improve the water metabolism after heart failure in rats.Methods:Except for the control group,the heart failure model was induced by isoproterenol injection,then the urine volume and the body weight were monitored.The model rats were randomly divided into the model group,10 ml/kg Shenfu group,20 mg/kg spironolactone group and the combination groups(20 ml/kg,10 ml/kg and 5 ml/kg Shenfu+20 mg/kg spironolactone).Before the rats were killed,the levels of AVP and NT-proBNP were detected in blood sampling from the aorta,the mRNA and protein expressions of AQP-2 and V_(2)R in the renal medulla were detected by quantitative PCR and Western blot.Results:During the modeling,compared with the control group,the weight and urine volume were increased in the model group(P<0.05),the serum levels of AVP and NT-proBNP were increased,the mRNA of V_(2)R was significantly up regulated,the expression of AQP-2 was up regulated(P<0.05 or P<0.01).After administration,compared with the model group,the urine volume in 20 mg/kg spironolactone group and all doses of combination groups were significantly higher than that in the model group(P<0.05),the AVP level was significantly decreased(P<0.05).Compared with the three combination groups,the protein expression of AQP-2 was significantly up regulated in other groups(P<0.05).Compared with the model group,the expression of V_(2)R was significantly down regulated in the control group,Shenfu group and three combination groups(P<0.05).Compared with the three combination groups,the expression of V_(2)R was significantly up regulated(P<0.05)in other groups.Conclusion:Shenfu injection can improve the water and sodium retention of rats with heart failure,mainly by reducing the expressions of AVP and its receptor V_(2)R,thus restoring the escape mechanism.Shenfu injection has a limited diuretic effect,which is weaker than spironolactone,and needs its com

关 键 词：参附注射液 心力衰竭 血管加压素逃避 水钠代谢 

分 类 号：R285.5[医药卫生—中药学]