| ObjectiveTo observe the clinical outcome of Erxian Decoction in the treatment of postmenopausal osteoporosis with kidney yang deficiency,and to explore the mechanism of Erxian Decoction in the treatment of postmenopausal osteoporosis through network pharmacological prediction and animal experiment verification.Methods1.From December 2019 to January 2021,90 patients with postmenopausal osteoporosis(kidney yang deficiency)in the outpatient department of Kunshan Affiliated Hospital of Nanjing University of traditional Chinese medicine were divided into control group and experimental group using random number table method.The control group was treated with Caltrate and alfacalcitol.The experimental group was treated with Erxian Decoction on the basis of the control group.The course of treatment was 12 weeks.The VAS score of low back pain,TCM syndrome score,quality of life score,bone mineral density and bone metabolism markers were observed before and after treatment.The obtained data were statistically analyzed to evaluate the clinical efficacy.2.Using the method of network pharmacology,the gene network of Erxian Decoction effective compound-miRNA target-postmenopausal osteoporosis was constructed,the core targets were screened,and the results were verified by clinical samples.3.The animal model of osteoporosis in ovariectomized mice was established.The protective effect of Erxian Decoction on bone loss caused by estrogen reduction was determined by means of microCT and histomorphology.Through the effect of Erxian Decoction containing serum on osteoclastic differentiation of osteoclast precursor cells and osteogenic ability of bone marrow mesenchymal stem cells,the mechanism of Erxian Decoction against postmenopausal osteoporosis was further clarified.Results1.After 12 weeks of treatment with Erxian Decoction Combined with calcium tablets and alfacalcidol,VAS score of low back pain and TCM syndrome score of kidney yang deficiency decreased,and SF-36 quality of life score increased.Serum bone formation markers(plnp and serum osteocalcin)increased,and serum bone resorption marker(?-CTX)and bone mineral density had no significant change.2.A total of 104 effective compounds,122 predicted microRNA targets and 171 disease genes of postmenopausal osteoporosis are obtained.The most important microRNA target in the network is mirna-335-5p,and its target genes are enriched in the regulation of osteogenesis and mineralization and regulation of osteoblast proliferation.Clinical sample verification showed that plasma mirna-335-5p in the experimental group increased 7.43 times compared with that before treatment,but there was no significant change in the control group.3.After treatment with Erxian Decoction,bone mineral density,bone volume fraction and number of trabeculae increased,and the separation of trabeculae decreased;The shape and structure of bone trabeculae were significantly improved;Serum P1NP increased,CTX decreased,and the expression of miRNA-335-5p increased.Erxian Decoction containing serum inhibited the gene expression of TRAP,CTSK and NFATc1 in osteoclasts,inhibited the formation of muscle protein ring in osteoclasts and reduced their bone resorption ability;Erxian Decoction containing serum promoted the activity of Bone Marrow Mesenchymal Stem Cells,increased the expression of miRNA-335-5p,decreased DKK1 and promoted Wnt/?-Catenin signal channel promotes ability differentiation of Bone Marrow Mesenchymal Stem Cells.Conclusion1.The short-term treatment of Erxian Decoction Combined with calcium tablets and alfacalcitol can alleviate low back pain,improve TCM symptoms of kidney yang deficiency,improve quality of life and increase bone formation,but there is no significant change in bone mineral density2.Erxian Decoction can regulate bone metabolism indexes,increase bone mineral density,inhibit bone loss and improve bone microstructure in ovariectomized mice.3.Erxian Decoction containing serum inhibits osteoclast formation and bone resorption by inhibiting osteoclast specific gene expression and actin ring formation.4.Erxian Decoction containing serum decreased DKK1 and activated Wnt/?-cateninsignal channel and promoted the osteogenic ability of Bone Marrow Mesenchymal Stem Cells by changing the expression of miRNA-335-5p... |
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