Objective To explore the molecular pathogenesis of Zuogui Pill in the prevention and treatment of postmenopausal osteoporosis in genomic level by analyzing bone marrow mesenchymal stem cells（ BMSCs） gene expression time sequence variation trend in osteoporosis model rats. Methods Senventy-two rats were randomly divided into sham operation group

model group

estradiol valerateand group and Zuogui Pill group

with 18 rats in each group. In addition to the sham operation group

the rats in the other groups were removed with bilateral ovary to establish the postmenopausal osteoporosis models. Two weeks after surgery

the estradiol valerateand group and the Zuogui Pill group were gavaged with estradiol valerateand tablets solution（ 0. 01 mg / ml） and Zuogui Pill solution（ 0. 5 g /ml） respectively

the rats in sham operation group and the model group were gavaged with the same volume of distilled water

with 1 ml /100 g each time

1 time a day until the 4th

8th

and 12 th weekend after surgery（ 6 rats at each time point）. At the end of the 12 th week

the bone mineral density of the distal femur bone

proximal tibia bone

and lumbar vertebrae bone of the rats in each group were detected. The femur bone and tibia bone of the rats in each group were parted under sterile environment

bone marrow mesenchymal stem cells were cultured

gene expression of BMSCs F2 cells in each group were detected by expression profile chip

differential expression genes（ DEGs） were selected by SPSS18. 0 software

and STEM method was used to analyze the time sequence

and Function and pathway enrichment was evaluated by DAVID. Results The bone mineral density of the distal femur bone

proximal tibia bone and the lumbar vertebrae bone of rats in the model group were significantly lower than those in the sham operation group（ P < 0. 01）; The bone mineral density of the 3 bone sites in the Zuogui Pill group and estradiol valerate group were higher than those in the model group（ P < 0. 05 or P < 0. 01）. In Zuogui Pill group

model group and the control group

time sequence significant trend DEGs is up to 56. At the end of the fourth week

genes Ppig

Rb1cc1

Il6 and Rock1 were significantly down regulated and were concentrated to cell proliferation

autophagy and apoptosis

signaling pathway and cell differentiation

etc. Conclusion Zuogui Pill can widely regulate expression of BMSCs gene through many ways

such as cell proliferation

autophagy and apoptosis

signal transduction

cell differentiation

etc.

which can finally reduce the loss of bone mass.