Resveratrol On Bone Metabolism In Type 1 Diabetic Mice

With the improvement of medical technology,the survival of patients with type 1diabetes is significantly prolonged,and its complications have gradually become the focus of attention,and bone damage of type 1 diabetes is one of them.Type 1 diabetes is mostly caused by adolescents or children,and the treatment experience and drugs for osteoporosis in this population are limited.Resveratrol(RESV)is a traditional Chinese medicine monomer.It has been found to have excellent anti-oxidant and anti-inflammatory effects and can promote osteogenic differentiation of bone marrow mesenchymal stem cells.Studies have shown that resveratrol repairs diabetes.Play an active role in rat bone injury.OBJECTIVE: This study aims to investigate the effects of resveratrol on bone damage in first-onset type 1 diabetes by constructing an osteoporosis animal model of type 1 diabetes,and provide valuable ideas and implications for clinical treatment of type1 diabetes leading to bone damage..METHODS: Twenty-four non-obese diabetic(NOD)mice were divided into 4 groups:diabetic group(DM group,n=6): intragastric administration with 0.9% sodium chloride solution;insulin group(INS group,n= 6): Subcutaneous injection of insulin glargine daily after onset,the dose is 0.2-0.4U/kg,adjusted according to the blood glucose of the day;resveratrol group(RESV group,n=6): on the third day after onset The RESV was administered at a dose of 200 mg/kg·d;after 8 weeks of feeding,the non-infected NOD mice were used as a normal control group(N group,n=6).After 8 weeks of treatment,blood was taken from the internal iliac vein,serum was collected,and serum acid phosphatase(TRACP)was detected by double antibody sandwich method(ELISA).The mice were sacrificed by cervical dislocation.The microstructure of the bone was observed by Micro-CT on the right femur.After decalcification of the left femur 10%ethylenediaminetetraacetic acid(EDTA),paraffin sections were made for alkaline phosphatase(ALP)staining.The expression levels of bone tissue related genes OCN,Runx2,PPAR-G and TRAP were detected by RT-PCR.RESULTS:(1)Micro-CT results showed a decrease in bone mineral density(BMD)in the diabetic group(P=0.015)and a decrease in bone volume percentage(BV/TV)compared with the normal group(P=0.049);compared with the diabetic group.Increased bone mineral density(BMD)in the resveratrol-treated group(P=0.008),increased bone volume percentage(BV/TV)(P=0.014),and increased bone surface density(BS/TV)(P=0.016)The structural model index(SMI)was elevated(P=0.029);the number of trabecular bone(Tb.N.)was significantly increased in the resveratrol-treated group compared with the insulin-treated group(P=0.018).The 3D reconstruction of bone micro-CT images showed that the trabecular bone shape of the diabetic group was blurred,the number was reduced,thinned,interrupted,the stump was free,and the trabecular spacing was widened.In the insulin treatment group and the resveratrol treatment group,the trabecular bones were connected to each other to form a body network,and the trabecular surface was smooth and the trabecular spacing was small.(2)ALP staining of bone tissue sections showed that the trabecular structure of the diabetic group was disordered and thinned,and the trabecular spacing was large.The trabecular structure of the insulin-treated group and the resveratrol-treated group was intact and continuous,compared with the diabetic group.The trabecular structure is intact,relatively thick,and the spacing of the trabecular bone is small.Comparing the number of osteoblasts between the groups,the results showed that the bone cells of diabetes were significantly reduced,and the number of bone cells composed of insulin treatment was slightly more than that of the resveratrol treatment group.(3)Real-time quantitative PCR(RT-PCR)results showed that the relative expression of TRAP and PPAR-G increased in the diabetic group(P=0.032;P=0.013);compared with the diabetic group,the insulin treatment group TRAP,PPAR-G The relative expression decreased(P=0.025;P=0.017),the expression of RUNX2 relative expression increased(P=0.030);the expression of TRAP and PPAR-G decreased in resveratrol treatment group(P=0.013;P=0.028)The expression of RUNX2 was increased(P=0.034).Conclusion: The number of osteoblasts caused by type 1 diabetes is decreased,osteogenic activity is weakened,osteoclast activity is enhanced,and bone marrow stem cell fatification is the main cause of secondary bone damage.Resveratrol can increase the number of osteoblasts and osteoblast activity,reduce bone resorption,and has a positive effect on the treatment of bone damage secondary to diabetes.