Objective To observe the effect of combined intervention of electroacupuncture(EA)and astragaloside IV(ASIV)on cardiac hypertrophy and transforming growth factorβ1(TGF-β1)/Smad signaling in isoproterenol(ISO)induced cardiac hypertrophy rats

so as to investigate its underlying mechanisms in improving myocardial fibrosis.Methods A total of50 SD rats were randomly divided into 5 groups:normal control

model(ISO)

Propranolol(PRO)

ASIV and EA+ASIV groups(n=10 in each group).The myocardial fibrosis model was established by intraperitoneal injection(i.p.)of ISO(10 mg·kg-1·d-1)

once daily for 30 days.Rats of the control group were given normal saline(i.p.)

those of the PRO group given with PRO(40 mg·kg-1·d-1

gavage)

and those of the ASIV and EA+ASIV groups were treated by gavage of ASIV(40 mg·kg-1·d-1)

once daily for 30 days.EA(20 Hz

6 V)was applied to bilateral"Neiguan"(PC 6)for 10 min

once every day for 30 d.The heart mass index(HMI

whole heart weight/body weight)and left ventricular(LV)mass index(LVMI

weight of the LV/body weight)were calculated to assess the state of cardiac hypertrophy.The enzyme linked immunosorbent assay(ELISA)was used to determine the levels of procollagen I carboxy-terminal propeptide(PICP

a marker of extracellular matrix remodeling)and carboxyterminal telopeptide of type I collagen(ICTP

a metabolite of type I collagen)in serum

and Western blot was used to test protein contents of TGF-β1

Smad 2/3

Smad 4

Smad 7 in the left ventricle tissue of the heart.Results After modeling

the HMI and LVMI

serum PICP and ICTP contents and the expression levels of myocardial TGF-β1

Smad 2/3 and Smad 4 proteins were significantly increased in the model(ISO)group(P<0.05)

suggesting a deposition of collagen and cardiac hypertrophy

and were considerably decreased in PRO

ASIV and EA+ASIV groups after the intervention(P<0.05).The expression level of myocardial Smad 7 protein was significantly lower in the model group than in the normal control group(P<0.05)

and significantly up-regulated in PRO

ASIV and EA+ASIV groups(P<0.05).Sirius Red staining of the left ventricular myocardium showed a dense deposition of collagen and a severer myocardial fibrosis in the model group

and a relatively lighter fibrosis in the PRO

ASIV and EA+ASIV groups.The therapeutic effects of EA+ASIV were comparable to those of PRO

and were significantly superior to those of ASIV in down-regulating HMI

serum ICTP

and myocardial Smad 2/3 and Smad 4 expression and up-regulating Smad 7 protein(P<0.05).There were no significant differences among the PRO

ASIV and EA+ASIV groups in LVMI

PICP and TGF-β1 levels

and between the PRO and EA+ ASIV groups in HMI

ICTP

Smad 2/3

Smad 4 and Smad 7 levels(P> 0.05).Conclusion EA stimulation of PC 6 combined with ASIV can relieve cardiac hypertrophy and myocardial fibrosis in rats

which may be associated with its effects in regulating myocardial TGF-β1/Smad signaling pathway.