Objective: To explore the protective mechanism of Shenfu Qiangxin pill(SFQX) on heart and kidney cells apoptosis in rats with cardio-renal syndrome (CRS) based on the (pro)rennin receptor (PRR)-mediated mitogen-activated protein kinase(MAPK) signal pathways. Method: Wistar rats underwent reperfusion injury combined with abdominal aortic constriction after renal ischaemia to prepare CRS models. The CRS rats were divided randomly into three groups:CRS model group (10 mL·kg-1pure water

ig);CRS+SFQX group (SFQX group

13.2 g·kg-1 SFQX

ig);CRS+Handle region peptide (HRP)group (10 mg·kg-1 HRP

iv). The rats in sham operation group were ig given with the same volume of pure water. Treatments were given 8 weeks after surgery

1 time/day

for 4 weeks. After the experiment

the rats were detected for brain natriuretic peptide (BNP)

urea nitrogen (BUN)

and creatinine (Cr) levels;ultrasound cardiograph for small animals was used to detect end diastolic interventricular septum thickness (IVS)

left ventricular end diastolic posterior wall thickness (LVPW) and left ventricular ejection fraction (LVEF);real time fluorescent PCR was used to measure PRR mRNA expressions of left ventricle and kidney;Western blot assay was used to determine MAPK signal pathways

including extracellular signal-regulated kinase 1/2 (ERK1/2)

C-Jun amino terminal kinase (JNK)

and P38 protein expressions;Terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) was used to detect cells apoptosis of left ventricular and renal tissues. Result: Compared to the sham operation group

serum BNP

BUN and Cr levels were significantly increased (P<0.05);IVS

LVPW levels were significantly increased (P<0.01);LVEF levels were significantly decreased (P<0.01);mass index of left ventricle was significantly increased (P<0.01);mass index of left kidney was significantly decreased in CRS rats(P<0.01).Expression of PRR mRNA was increased (P<0.01);protein expressions of ERK1/2

p38 and JNK were increased (P<0.01). Myocardial and renal cell apoptosis rate was 32.5% and 63.2% respectively.SFQX 13.2 g·kg-1could significantly reduce cardiac hypertrophy in CRS rats

inhibit IVS and LVPW

increase EF

significantly decrease BUN and Cr

decrease PRR mRNA expression and ERK1/2

P38 protein expression of injured tissues

and decrease the myocardial and renal cell apoptosis rate. Conclusion: SFQX could improve the heart and kidney function of CRS rats

and reduce myocardial and renal cell apoptosis through reducing PRR mRNA expression of myocardial and renal cells and inhibiting ERK1/2

JNK and P38 phosphorylation in MAPK signal pathways.