| Objective:To investigate the role of GABA Signalling in the formation and development of OP and explore the effect of total flavonoids of Rhizoma Drynariae(TFRD) on it.Methods:1.45 female SD rats of 3-month old were randomly divided into operation group(30 rats) and sham operation group(15 rats). The osteoporotic model was established by ovariectomy.12 weeks after ovariectomy, when the OP was affirmed by dualenergy X-rayabsorptiometry the rats in operation group were randomly divided into model group(15 rats) and treated group(15 rats).2. According to the dose conversion between rat and human, the rats in the treated group were respectively treated with gastric perfusion of TFRD solution that amounted to the dose that used in clinic adult patients and those in the sham operation group and model group received gastric perfusion of normal saline. The gastric perfusion will last for 12 weeks.3. We got the bone mineral density(BMD) through dual-energy X-ray measurement and the levels of serum GAD was obtained by ELISA. Then, the expression of GABA, GABABR1 and GAT1 of distal femur was checked with immunohistochemical techniqueand and reverse transcription polymerase chain reaction (RT-PCR) was applied to detect the the expression of GABABRI mRNA of femur. Results:1.12 weeks after ovariectomy, the BMD of different parts of rats in model group was significantly lower than that of rats in sham operation group(P<0.05).2. When the 12 weeks'gastric perfusion ended, the levels of serum GAD of rats in model group was significantly higher than that of sham operation group(P< 0.05). While the levels of serum GAD of rats in treated group was significantly lower than that of model group(P<0.05), and there was no significantly difference between sham operation group and treated group(P>0.05).3. When the 12 weeks'gastric perfusion ended, the expression of GABA and GABABRI of distal femur of rats in model group was significantly stronger than that of sham operation group(P<0.05). While the expression of GABA and GABABRI of distal femur of rats in treated group was significantly weaker than that of model group(P<0.05), and there was no significantly difference between sham operation group and treated group(P>0.05).4. When the 12 weeks gastric perfusion ended, there was no significantly difference in the three groups(P>0.05).5. When the 12 weeks'gastric perfusion ended, the expression of GABABRI mRNA of femur of rats in model group was significantly stronger than that of sham operation group(P<0.05). While the expression of GABABRI mRNA of femur of rats in treated group was significantly weaker than that of model group(P<0.05), and there was no significantly difference between sham operation group and treated group(P>0.05). Conclusions:1. It is suggested that the high levels of serum GAD and the up-regulated expression of GABA, GABABRI, GABABRI mRNA of bone may be one of the evidences that the GABA signalling was involved in development of OP.2. The intervention of TFRD can reduce the abnormally levels of serum GAD and the up-regulated expression of GABA, GABABRI, GABABRI mRNA of bone, which may be one of the mechanisms of its treatment on OP. |
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