当归芍药散对慢性心力衰竭大鼠机体水液代谢障碍的作用及其机制

目的 探讨当归芍药散对慢性心力衰竭（chronic heart failure，CHF）大鼠机体水液代谢障碍的影响及作用机制。方法 将72只大鼠随机分为正常组，模型组，芪苈强心胶囊组，当归芍药散低、中、高剂量组，每组12只，最终正常组，模型组，芪苈强心胶囊组，当归芍药散低、中、高剂量组纳入实验的大鼠数分别为8、6、8、7、8、8只。采用少量多次腹腔注射阿霉素复制CHF大鼠模型。给药4周后，采用心脏彩色多普勒超声仪测定各组大鼠左心室射血分数（left ventricular ejection fraction，LVEF）、左心室短轴缩短率（left ventricular fractional shortening，LVFS）；HE染色观察心肾组织损伤情况；全自动生化分析仪检测心功能和肾功能指标［肌酸激酶（creatine kinase，CK）、肌酸激酶同工酶（creatine kinase isoenzyme，CK-MB）、乳酸脱氢酶（lactate dehydrogenase，LDH）、血清肌酐（serum creatinine，SCr）、尿素氮（urea nitrogen，BUN）］，同时测定24 h尿量、腹水质量以及脏器指数等水液代谢指标；ELISA法测定大鼠血清N端脑钠肽前体（N-terminal pro-brain natriuretic peptide，NT-proBNP）水平以及一氧化氮合酶（nitric oxide synthase，NOS）活性及一氧化氮（nitric oxide，NO）、环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）含量；免疫组织化学法检测大鼠心肌组织中水通道蛋白（aquaporin，AQP）1、AQP4和肾组织中AQP2表达水平；Western blot法检测大鼠心肌组织中诱导型一氧化氮合酶（inducible nitric oxide synthase,iNOS）、AQP1、AQP4和肾组织中iNOS、AQP2表达水平。结果 当归芍药散可改善CHF大鼠心肾功能，减少血清NT-proBNP、NO水平（P＜0.05）；调节CHF大鼠24 h尿量、腹水等水液代谢指标以及脏器指数，改善心肌组织病理变化；降低心脏组织iNOS、AQP1、AQP4及肾组织中iNOS、AQP2表达水平（P＜0.05）。结论 当归芍药散能够改善CHF引起的水液代谢障碍，保护CHF大鼠的心肾功能，其作用机制可能与抑制NO的过度分泌，下调AQP1、AQP4、AQP2蛋白的表达水平有关。

Effect of Danggui Shaoyao San on Fluid Metabolism Disorder in Rats with Chronic Heart Failure and Its Mechanism

Objective To investigate the effect of Danggui Shaoyao San (DSS) on fluid metabolism disorder in rats with chronic heart failure (CHF) and its mechanism of action. Methods A total of 72 rats were randomly divided into normal group, model group,Qili Qiangxin Capsule group,and low-, middle-, and high-dose DSS groups, with 12 rats in each group, and finally 8, 6, 8, 7, 8, and 8 rats, respectively, in these groups were included in experiment. Repeated intraperitoneal injection of a small amount of adriamycin was performed to establish a rat model of CHF. After administration for 4 weeks, cardiac color Doppler ultrasound was used to measure left ventricular ejection fraction and left ventricular fractional shortening; HE staining was used to observe cardiac and renal injury; an automatic biochemical analyzer was used to measure cardiac function and renal function parameters, including creatine kinase, creatine kinase-MB, lactate dehydrogenase, serum creatinine, and blood urea nitrogen, and related fluid metabolic markers were also measured, including 24-hour urine volume, ascites, and visceral index; ELISA was used to measure the serum level of N-terminal pro-brain natriuretic peptide (NT-proBNP), the activity of nitric oxide synthase, and the content of nitric oxide (NO) and cyclic guanosine monophosphate; immunohistochemistry was used to measure the expression of aquaporin 1 (AQP1) and aquaporin 4 (AQP4) in myocardial tissue and aquaporin 2 (AQP2) in renal tissue; Western blot was used to measure the expression of inducible nitric oxide synthase (iNOS), AQP1, and AQP4 in myocardial tissue and the expression of iNOS and AQP2 in renal tissue. Results DSS significantly improved the cardiac and renal function of CHF rats and reduced the serum levels of NT-proBNP and NO (P<0.05). It could also regulate the fluid metabolic markers such as 24-hour urine volume, ascites, and visceral index and improve the pathological changes of myocardial tissue. In addition, it significantly reduced the expression of iNOS,AQP1, and AQP4 in myocardial tissue and the expression of iNOS and AQP2 in renal tissue (P<0.05). Conclusion DSS can improve fluid metabolism disorder caused by CHF and protect the cardiac and renal function of CHF rats, possibly by inhibiting the excessive secretion of NO and downregulating the protein expression of AQP1,AQP4, and AQP2.