Objective: To observe the effect of Banxia Baizhu Tianma Tang (BBT) on Mitogen-activated protein kinase (MAPK) signaling pathway of myocardial hypertrophy of hypertensive rats with the syndrome of excessive accumulation of phlegm-dampness (EAPD)

and explore the pathological mechanism of alleviating myocardial hypertrophy. Method: Spontaneous hypertensive rats (SHRs) were fed with high-fat diet for 20 weeks to establish hypertensive EAPD rat models (HEAPD). Other 10 SHR and WKY rats were included into control groups. Both groups were fed for 20 weeks. After 20 weeks

the modeled rats were divided into high dosage BBT decoction group (13.8 g·kg-1·d-1)

low dosage BBT decoction group (6.90 g·kg-1·d-1)

telmisartan group (6.33 g·kg-1·d-1) and model group (equivalent normal saline). SHR and WKY control groups were intragastrically administrated with equivalent normal saline for 12 weeks. Body weight and blood pressure were measured every week. Left ventricular end diastolic diameter (LVEDd)

left ventricular posterior wall diameter (LVPWd)

interventricular septal diameter (IVSd)

left ventricular ejection fraction (LVEF) were observed by echocardiography every two weeks. Left ventricular mass (LVM) and left ventricular mass index (LVMI) were calculated. AngiotensinⅡ (AngⅡ)

tumor necrosis factor alpha (TNF-α)

interleukin 6(IL-6)

nitric oxide (NO) in myocardial homogenate were determined by ELISA. Morphological changes of left ventricular observed by HE staining. The distributions of angiotensin II type 1 receptor (AT1) were detected by immuonhistochemical staining assay. Levels of mRNA expression of angiotensin converting enzyme(ACE)

AT1

proto-oncogene serine/threonine-protein kinase(c-Raf)

extracellular regulated protein kinases 1(ERK 1)

ERK-2 were determined by real-time PCR. The expression of p-c-Raf and p-ERK1/2 were observed by Western blot. Result: EAPD rat models were established successfully after high fat diet for 20 weeks. After drug administration for 12 weeks

compared with SHR model group

weight of both high and low dosage BBT groups and telmisartan group was significantly lower (P<0.05)

blood pressure of high dosage BBT group and telmisartan group was decreased significantly (P<0.05) in the fourth week

while blood pressure of low dosage BBT group was decreased significantly (P<0.05) in the eighth week. IVSd

LVPWd

LVM

LVMI of high dosage BBT group and telmisartan group were decreased significantly

while LVEDd increased (P<0.05);AngⅡ

TNF-α

IL-6 in myocardium of high dosage BBT group and telmisartan group were decreased significantly (P<0.05)

while NO increased significantly (P<0.05). NO of low dosage BBT group increased significantly (P<0.05). The myocardial morphology of high dosage BBT group and telmisartan group was improved

and the distribution of AT1 was decreased in different degrees after drug treatment. Levels of mRNA expression of ACE

AT1

c-Raf

ERK1 and ERK2 of high dosage BBT group and telmisartan group were decreased significantly (P<0.05). The protein expression of p-c-Raf and p-ERK1/2 of both BBT high and low dosage groups and telmisartan group were decreased significantly (P<0.05). Conclusion: BBT decoction can alleviate cardiac hypertrophy in HEAPD. The possible mechanism may be correlated with the down-regulation of MAPK pathway and the inhibition of RASs.