Inhibitory Effect of Rutaecarpine on Left Ventricular Hypertrophy Rat Model Induced by Abdominal Aorta Coarctation / 医药导报

ABSTRACT

Objective To investigate the inhibition of rutaecarpine (Rut) on left ventricular hypertrophy rat induced by abdominal aorta coarctation (AAC) and further explore the potential mechanisms. Methods Left ventricular hypertrophy was induced by AAC in male Sprague-Dawley rats.Fifty rats were randomly divided into five groupsmodel control group,sham operation group,low-,middle- and high-dose (10,20,40 mg?kg-1?d-1 ) Rut group,with 10 rats of each group.Rut was administrated by gavage once daily from the first day after operation for consecutive 4 weeks.The sham operation and model groups were administrated with equal volume of 0.9％ sodium chloride solution.The hemodynamics parameters were detected by BL-420 E biology function laboratory system,and the left ventricular hypertrophy index (LVHI,left ventricular weight/ body weight) was measured at 8 h after administration of the last dose.The pathological changes of left ventricular hypertrophy were evaluated by HE staining.To elucidate the mechanism of protection,the mRNA expressions of atrial natriuretic factor ( ANF),extracellular signal-regulated kinase 2 (ERK2) and MAPK phosphatase-1 (MKP-1) were analyzed by real time RT-PCR,and the protein expressions of MKP-1 and phosphorylated ERK2 (p-ERK2) were examined by Western blotting. Results Left ventricular hypertrophy induced by AAC was evidenced by the increased left ventricular weight (LVW) and LVHI (P<0.01),the decreased± dp/ dt max (P<0.01),and the elevated expression of ANF (P<0.01).Compared with model control,Rut (20,40 mg?kg-1?d-1 ) treatment significantly attenuated AAC-induced rat left ventricular hypertrophy,decreased the LVHI (P<0.05),left ventricular systole pressure (LVSP),and left ventricular end diastolic pressure ( LVEDP ) ( P < 0. 05), and increased ± dp/ dtmax ( P < 0. 01). In addition, Rut ( 20, 40 mg?kg-1?d-1 ) downregulated the expression of ANF,ERK2 mRNA,and ERK2 protein,but upregulated the MKP-1 mRNA and protein expression.However,Rut low-dose (10 mg?kg-1 ?d-1 ) was ineffective (P> 0.05). Conclusion Rut alleviates left ventricular hypertrophy induced by abdominal aorta coarctation,and the protection appears to be due,at least in part,to its inhibitory effects on the MAPK/ ERK signal pathway.