Based On OPG/RANKL/RANK Signal Pathway,to Explore The Mechanism Of Uyghur Medicine Qushi Jiangu Formula In The Intervention Of Postmenopausal Osteoporosis In Rats

Objective:Based on the OPG/RANKL/RANK signaling pathway,the effect and mechanism of Uighur medicine to remove moisture and bone strengthening prescription in postmenopausal osteoporosis rats and its mechanism..Method:1)70 SD rats were randomly divided into 7groups of 10.Bilateral ovarianectomy was performed to establish a rat model of postmenopausal osteoporosis（PMOP）;2)The positive control group was given Bujiale by gavage,the rats in each dose group of Qushi Jiangu Formula were given corresponding doses of medication by gavage,and the other groups were given distilled water intervention for 9 weeks;3)Micro-CT was used to detect bone density,three-point bending method was used to detect biomechanical properties,and HE staining method was used to observe bone trabecular changes;ELISA detected serum estrogen（E2）,calcium（Ga）,phosphorus（Pi）,bone-specific alkaline phosphatase（BALP）,parathyroid hormone（PTH）,1,25 dihydroxyvitamin D3（1,25（OH）₂D₃）,type I collagen cross-linked N-terminal peptide（NTX）,anti-tartaric acid phosphatase（TRACP-5b）,type I collagen cross-linked C-terminal peptide（CTX）,osteopryptin（OPG）,RANKL,RANK;Immunohistochemistry measured the content of 1αhydroxylase,OPG and RANKL protein in the kidney.4)One-way ANOVA was used,and P<0.05 was used as the test standard with significant differences.Results:1)Compared with the normal control group and the sham surgery group,the bone density decreased（P<0.01）,the bone morphometric parameters changed（P<0.01）,and the biomechanical properties decreased significantly（P<0.01）in the OVX model group;the thickness and spacing of the bone trabeculae in the OVX model group decreased under light microscopy,and there were significant microfractures and bone defects formed by post-fracture resorption;serum E2,Ca,1,25（OH）₂D₃,OPG,and BCAP content decreased（P<0.01）,Pi,PTH,RANKL,The content of RANK,CTX,NTX,TRACP-5b was increased（P<0.01）,and the content of1α-hydroxylase protein decreased（P<0.01）.2)The bone density of the drug group was improved to varying degrees,bone morphometric parameters changed,bone biomechanics improved,histopathology changed,and serum bone metabolism index disorder was improved.Among them,the high-dose group had a better effect,and the efficacy was close to that of the positive control group.Compared with the OVX model group,bone density increased（P<0.01）,bone volume percentage,bone surface area,bone surface density and number of bone trabeculae were significantly increased,bone surface area to volume ratio and trabecular separation decreased significantly（P<0.01）,and the fracture energy（P<0.05）,ultimate load,stiffness,elastic modulus and ultimate stress（P<0.01）were significantly increased.The pathological sections showed that the high-dose group had better intertrabecular connections,more complete and uniform thickness,and rare trabecular fracture and fracture marks.3)The content of serum E2,Ca,1,25（OH）₂D₃,OPG（P<0.01）and BLAP（P<0.05）increased,the content of Pi,PTH,CTX,NTX,TRACP-5b,RANKL and RANK decreased significantly（P<0.01）;4),the expression content of 1α-hydroxylase in the kidney increased significantly（P<0.01）,the content of OPG decreased significantly（P>0.05）,and the content of RANKL decreased significantly（P<0.01）;Conclusion:Uyghur medicine can effectively improve the bone density of PMOP model rats,optimize bone microstructure,optimize bone biomechanical properties,give full play to the role of prevention and treatment of PMOP,the mechanism of action may be by increasing estrogen levels,activating OPG/RANKL/RANK pathway,upregulating the expression of OPG,inhibiting the expression of RANKL,estrogen promoting the activation of renal 1α-hydroxylase,regulating calcium and phosphorus metabolism to play a synergistic effect,and improving the high bone generation conversion level of ovary model rats.Thereby promoting bone formation,inhibiting bone resorption,and preventing osteoporosis.