Objective:To study effect and mechanism of Zuogui Wan in ovariectomized osteoporosis rats. Method: SD female rats were divided into 7 groups: normal

Sham operation (Sham)

ovariectomized(OVX)

Zuogui Wan high-[ZG(H)]

Zuogui Wan middle-dose[ZG(M)]

Zuogui Wan low-dose[ZG(L)] and nilestriol(N). The rat overiectomy-induced osteoporosis model was adopted

21 days later

normal

Sham and OVX rats were ig given with dwas？ tilled water. ZG(H

M

L) rats groups were ig given with Zuogui Wan at dosage of 6.4

3.2

1.6 g·kg-1

once per day. N rats were ig given with 0.021 g·kg-1

once per week. Sixty days later

the left hind distal femur at the 1/3 side was taken to test the pathological section for determining the percentage of trabecular separation (Tb·Ar). We determined the bone mineral density (BMD) of right hind proximate femur at the 1/3 and used the method of RT-PCR to test the expression of TGF-β1/Smad4 mRNA in kidney medulla. Result: Compared with OVX

ZG(H) and ZG(M) increased Tb·Ar and (P<0.05). No pathological change in kidney tissues was found. Compared with normal group

the expression of TGF-β1/Smad4 mRNA in OVX rats increased(P<0.05). Compared with OVX

the expression of TGF-β1/Smad4 mRNA in Zuogui Wan treated groups was down-regulated (P<0.05)

which was more significant in the total groups of Zuogui Wanl than that in nilestriol group

and low dosage of Zuogui Wan showed a most obvious down-regulation. Conclusion: Zuogui Wan can prevent and treat postmenopausal osteoporosis(PMOP)effectively. One of the mechanisms may be related to its interfering the TGF-β1/Smad4 signaling of the kidney tissue.