真武汤合苓桂术甘汤改善心肾综合征大鼠模型水钠潴留的作用机制研究

Mechanism of Zhenwu Decoction and Linggui Zhugan Decoction in improving water-sodium retention in rat model of cardiorenal syndrome

关键词:  真武汤合苓桂术甘汤  心肾综合征  大鼠  水通道蛋白2  异丙肾上腺素  5/6肾切除

Key words:  Zhenwu Decoction and Linggui Zhugan Decoction  cardiorenal syndrome  rats  aquaporin 2  isoproterenol  5/6 renectomy

摘要:

[目的] 研究真武汤合苓桂术甘汤对心肾综合征大鼠模型水钠潴留的作用机制。[方法] 将60只雄性SD大鼠随机分为两组，即空白组与手术组，空白组大鼠常规饲养，手术组大鼠经5/6肾切除联合异丙肾上腺素皮下注射制备心肾综合征模型，剔除死亡大鼠后，将手术组剩余成模大鼠按体质量分层随机分为空白组、中药组、常规治疗组。中药组给予真武汤合苓桂术甘汤灌胃，给药量为7.29 g生药/（kg·d）；常规治疗组给予贝那普利（0.45 mg/kg）+呋塞米（1.8m g/kg）；空白组予以等容积生理盐水灌胃，每日1次，连续6周。观察实验过程中各组大鼠的精神状态、活动情况、灵敏度、毛发情况、食欲、大小便等一般情况及死亡情况，比较各组灌胃前、灌胃6周后的血清脑钠肽（BNP）、血肌酐（Scr）、血尿素氮（BUN）、尿水通道蛋白2（AQP2）的前后差值情况。[结果] 灌胃6周后，中药组大鼠一般情况较灌胃前改善、喘息不明显，常规治疗组一般情况同样较灌胃前改善。通过比较治疗前后各组大鼠实验室指标差值发现，中药组与常规治疗组BNP均下降，中药改善大鼠心力衰竭情况接近常规治疗组水平，两组下降水平无统计学差异（P>0.05）；中药组Scr水平较前下降，常规治疗组Scr水平升高；中药组尿AQP2水平较前略增高，与空白组尿AQP2水平无统计学差异（P>0.05），常规治疗组尿AQP2水平较前明显升高。[结论] 心肾综合征大鼠尿AQP2的表达主要由肾脏调控，AQP2可作为心肾综合征水钠潴留状态的参考指标，真武汤合苓桂术甘汤改善心肾综合征大鼠水钠潴留状态的作用机制可能是通过抑制大鼠肾脏AQP2过度表达，减少水的重吸收，改善了水钠潴留状态。

Abstract:

[Objective] To study the mechanism of Zhenwu Decoction and Linggui Zhugan Decoction on water and sodium retention in rats with cardiorenal syndrome.[Methods] The 60 SD rats were randomly divided into two groups,the blank group and the operation group. Cardiorenal syndrome model was established by 5/6 nephrectomy combined with subcutaneous injection of isoproterenol in rats of operation group. After eliminating the dead rats,the remaining rats in the operation group were randomly divided into model group,traditional Chinese medicine group (TCM group) and conventional treatment group according to body weight. Rats in the TCM group were received 7.29 g crude drug/(kg·d)for intragastric administration. The routine treatment group was given benazepril[0.45 mg/(kg·d)] and furosemide[1.8 mg/(kg·d)]. The blank group and model group were intragastrically administered with normal saline of equal volume. They were given once a day for 6 consecutive weeks. The mental state,activity,sensitivity,hair condition,appetite,urine and feces and mortality of rats in each group were observed during the experiment. The difference of serum brain natriuretic peptide (BNP),serum creatinine (Scr),serum urea nitrogen (BUN) and urinary aquaporin 2 (AQP2) before and 6 weeks after gastric administration were compared.[Results] After 6 weeks of intragastric administration,the general situation of rats in the TCM group was better than that before gastric administration,and the wheezing was not obvious. The general situation of rats in the conventional treatment group was also better than that before gastric administration. By comparing the difference of laboratory indexes of rats before and after treatment,it was found that BNP in the TCM group and the conventional treatment group decreased,and the improvement of heart failure in the TCM group was close to the level of the conventional treatment group. There was no significant difference between the two groups (P>0.05). The level of Scr in TCM group was lower than before,while that in the conventional treatment group was higher. The level of AQP2 in urine of TCM group was slightly higher than before. There was no significant difference in urinary AQP2 level between TCM group and blank group (P>0.05). The level of urinary AQP2 in routine treatment group was significantly higher than that before.[Conclusion] The expression of urinary AQP2 in rats with Cardiorenal Syndrome is mainly regulated by the kidney,AQP2 can be used as a reference index for water and sodium retention in patients with cardiorenal syndrome. Zhenwu Decoction and Linggui Zhugan Decoction can improve the state of water and sodium retention in rats with cardiorenal syndrome. It may be through inhibiting the excessive expression of AQP2 in the kidney of rats, reducing the reabsorption of water and improving the state of water and sodium retention.