济阴决渎强心方对心肾综合征模型大鼠水钠排泄的影响

Effect of Jiyin Juedu Qiangxin Formula on the Excretion of Water and Sodium in Rats with Cardiorenal Syndrome

目的观察济阴决渎强心方对心肾综合征(CRS)大鼠水钠排泄的影响。方法采用冠状动脉结扎联合3/4肾脏切除术复制CRS大鼠模型。将30只造模成功大鼠按随机数字表法分为模型组、奥美沙坦酯组及济阴决渎强心方组,每组10只。另设9只SD大鼠为假手术组。以济阴决渎强心方[2 g/(100 g·d)]和奥美沙坦酯[0.3 mg/(100 g·d)]为干预手段,模型组和假手术组予饮用水每天2 mL灌胃,疗程28天。检测大鼠尿液指标,称量大鼠体重,检测血清学指标和心肾功能,计算分析指标间的相关性,HE染色后于光镜下观察肾脏组织病理学改变。结果与假手术组比较,模型组24 h尿量(24 h-UV)、24 h尿水通道蛋白2(24 h AQP-2)、体重、血清Cl-、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)降低(P<0.05,P<0.01),尿钠浓度(UNa)、尿微白蛋白(UMA)、尿微白蛋白与肌酐比值(ACR)、血清尿素氮(BUN)、血肌酐(SCr)、左心室收缩末内径(LVESd)、左心室舒张末内径(LVEDd)升高(P<0.05,P<0.01),病理显示模型组肾小球萎缩、肾小管上皮细胞萎缩、肾静脉扩张。与模型组比较,奥美沙坦酯组和济阴决渎强心方组B型脑钠肽(BNP)水平降低(P<0.05),LVEF升高(P<0.05,P<0.01);济阴决渎强心方组ACR、BUN、SCr、血清Na+水平降低(P<0.05,P<0.01),LVFS升高(P<0.01)。与奥美沙坦酯组比较,济阴决渎强心方组BUN、SCr降低(P<0.05,P<0.01),LVEF、LVFS升高(P<0.05)。与模型组比较,各干预组肾小球、肾小管结构改善。经相关性分析发现,24 h-UV与尿钠排泄率(UNaV)呈正相关(r=0.39,P<0.05),UNaV与24 h AQP-2呈正相关(r=0.40,P<0.05),24 h AQP-2与LVEF呈正相关(r=0.39,P<0.05)。结论济阴决渎强心方能改善CRS大鼠ACR、BUN、SCr、BNP、LVEF,改善肾脏组织病理损伤,增加AQP-2排出的作用,可能是改善心肾功能,增加水钠排泄的原因之一。

Objective To observe the effect of Jiyin Juedu Qiangxin Formula(JJQF)on the excretion of water and sodium in cardiorenal syndrome(CRS)rats.Methods The CRS model was established by coronary artery ligation combined with 3/4 nephrectomy.According to the random digit table,totally successfully modeled 30 rats were randomly divided into model group,olmesartan medoxomil group and JJQF group,with 10 rats in each group.Another 9 SD rats were selected as a sham operation group.Rats in the JJQF group were intragastrically administered with JJQF(2 g·100 g-1·d-1),and rats in the olmesartan medoxomil group were intragastrically administered with olmesartan medoxomil(0.3 mg·100g-1·d-1).Rats in the sham operation group and model group were given drinking water(2 mL/d).The medication lasted for 28 successive days.The urine indexes of rats were detected.The weight of rats was weighed.The serological indexes and heart and kidney function were detected.The correlation between each index was calculated and analyzed.The pathological changes of the kidney were observed under a light microscope after HE staining.Results Compared with the sham operation group,the levels of the 24 h urine volume(24 h-UV),24 h aquaporin 2(24 h AQP-2),Weight,Cl-,left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)in the model group decreased(P<0.05,P<0.01),while urine sodium concentration(UNa),urine microalbumin(UMA),urine microalbumin to creatinine ratio(ACR),serum urea nitrogen(BUN),serum creatinine(SCr),left ventricular end systolic diameter(LVESd),left ventricular end diastolic diameter(LVEDd)increased(P<0.05,P<0.01).The pathological results showed glomerular atrophy,renal tubular epithelial cell atrophy and renal vein dilatation in the model group.Compared with the model group,the level of B-type natriuretic peptide(BNP)decreased(P<0.05),and LVEF increased(P<0.05)in olmesartan medoxomil group and JJQF group.The levels of ACR,BUN,SCr and serum Na+decreased(P<0.05,P<0.01),while LVFS increased(P<0.01)in JJQF group.Compared with olmesartan medoxomil group,BUN and SCr decreased(P<0.05,P<0.01),LVEF and LVFS increased(P<0.05)in JJQF group.Compared with the model group,the structure of glomeruli and renal tubules in the intervention group was improved.The correlation analysis showed that 24 h-UV was positively correlated with urine sodium edcretion(UNaV)(r=0.39,P<0.05),UNaV was positively correlated with 24 h AQP-2(r=0.40,P<0.05),and 24 h AQP-2 was positively correlated with LVEF(r=0.39,P<0.05).Conclusion JJQF can improve ACR,BUN,SCr,BNP and LVEF,and improve renal tissue pathological damage,and increase AQP-2 excretion in CRS rats,which may be one of the reasons for improving heart and kidney function and increasing water and sodium excretion.