The Protectave Effects And Mechanisms Of Resveratrol On Estrogen Deficiency-induced Osteoporosis And Depressive-like Behaviors

Objective:To study the effects of resveratrol on osteoporosis and depression-like behaviors in ovariectomized rats.To explore the mechanism of resveratrol in improving osteoporosis and depression-like behaviors.Methods:In vivo:1.60 6-month-old female SD rats of SPF were randomly divided into 6 groups:(1)Sham(n=10);(2)Model group(n=10);(3)Resveratrol low dose group(n=10):resveratrol 50 mg.kg/d;(4)Resveratrol medium dose group(n=10):resveratrol 100 mg.kg/d;(5)Resveratrol high dose group(n=10):resveratrol 200 mg.kg/d;(6)Estrogen group(n=10):estradiol 0.08mg·kg/d.The animal model of postmenopausal osteoporosis was established by one-time removal of bilateral ovaries in rats.After 12 weeks of drug intervention,the weight of rats and uterus were compared.Bone structural and mineral changes were assessed by Micro-computed tomography(Micro-CT)and HE staining.Depression-like behaviors were assessed by the open field test,the sucrose preference test and Novelty-suppressed feeding test.Monoamines were detected by ELISA in the serum and brain regions after drug intervention.In vitro:1.MC3T3-E1 cells were treated with different concentrations of resveratrol.After 21 days,the number of calcium nodules in osteoblasts was compared by alizarin red staining to observe the effect of Resveratrol on the osteogenic differentiation of MC3T3-E1 cells.The expression of ERK/Wnt/?-catenin signaling pathway proteins was detected by using western blotting.2.PC12 cells were treated with 200 pM of corticosterone in the absence or presence of different concentrations of resveratrol.Then,cell viability was measured by Cell Counting Kit-8 assay.Apoptosis of PC 12 cells was measured by Annexin V-FITC and Propidium iodide(PI)labelling.The expression of apoptosis-related proteins including Bax,Bcl-2,caspase-3 was determined by western blotting.Results:1.After 12 weeks of treatment,resveratrol could significantly protect the microstructure of bone in the osteoporosis model induced by ovariectomy in low and middle dose groups.The mechanism may be related to that resveratrol can regulate ERK/Wnt/?-catenin signaling pathway-related proteins to promote osteoblast differentiation.Ovariectomized rats were observed to suffer from depression-like behaviors after 12 weeks,while resveratrol groups ameliorated depression-like behaviors and increased the level of monoamine neurotransmitters in the brain.The results showed that treatment with 200 ?M of corticosterone induced cytotoxicity in PC12 cells.However,different concentrations of RES(2.5?mol/L,5?mol/L and 10?mol/L)significantly increased the cell viability,suppressed the apoptosis of PC 12 cells,down-regulated Bax and caspase-3 protein expression,and up-regulated Bcl-2 protein expression.Conclusion:Osteoporosis and depression-like behaviors in OVX rats were attenuated by RES administration.The possible mechanism of anti-osteoporosis effect of resveratrol is related to the regulation of ERK/Wnt/?-catenin signaling pathway on osteoblasts.The mechanism of antidepression effect of resveratrol is related to the regulation of monoamine neurotransmitter levels in the brain and the neuroprotective effect.