| Objective To explore the mechanism of Zuogui Pill, a traditional Chinese medicine for tonifying the kidney, in treating ovariectomized osteoporosis in rats based on the Hedgehog signaling pathway. Methods Female SD rats were randomized into 3 groups: the blank control group, the sham operation group, and the model group. The ovaries of the model group rats were removed. In the sham operation group, only a small amount of fat tissue around the ovary was removed. After 12 weeks, the model group was randomly divided into 3 groups: the OVX group, the positive control group, the Zuogui Pill group. The positive control group was perfused with estradiol valerate suspension, the Zuogui Pill group was perfused with Zuogui Pill decoction, and the other groups were perfused with equal volume pure water. After 13 weeks, the rats were anesthetized and killed, their tibia and femur were taken. The Bone Mineral Density (BMD) of each group was detected by micro CT; The expression of the key factors of the Hedgehog signaling pathway, OPG and RANKL in bone marrow stromal cells of tibia was detected by immunohistochemistry (IHC). Results BMD in the sham operation group was higher than that in OVX group, the positive control group and the Zuogui pill group, and BMD in OVX group was lower than that in the positive control group and the Zuogui pill group .The expression levels of Ihh, Ptch, Smo, GLi1 and the ratio of RANKL/OPG in the OVX group were higher than that in the sham operation group; The protein expression levels of Ihh, Ptch, Smo, GLi1 and the ratio of RANKL/OPG in the positive control group and the Zuogui pill group were lower than those in the OVX group, but still higher than those in the sham operation group. Conclusion Zuogui Pill can inhibit the abnormal activity of Hedgehog signaling pathway caused by ovariectomy, and significantly reduce the expression level of key factors Ihh, Ptch, Smo and GLi1; Further, it can reduce the ratio of RANKL/OPG, inhibit the activity of osteoclasts(OC) and prevent bone loss. |