The Role Of SIRT1/NF-κB Signal Pathway In Vascular Inflammation Improved By Aerobic Exercise In Diabetic Rats

Background and purpose:Vascular complications induced by diabetes is the primary cause of death and disability resulted from diabetes.Inflammatory reaction run through pathogenic process of vascular pathology,and is the main mechanism of vascular diseases.therefore,it is important significance to prevent and treat vascular inflammation for diabetic vascular complications.At present,reducing glucose is the main therapy method for diabiets.Metformin is the biguanides medicine used widely in the control of blood glucose.Regular exercises can reduce body’s chronic inflammation,and have a protective effect on cardiovascular diseases.But its mechanism is still not well understood.This study intends to compare effects of aerobic exercise and metformin on vascular inflammation in diabetic rats by intervention of aerobic exercise and metformin.The mechanism of exercise on vascular inflammation in diabetic rats will be explored from the role the role of SIRT1/NF-κB signaling pathway in aerobic exercise by the methods of molecular biology.Methods:Fat food fed and low-dose STZ treated type 2 diabetic rats as animal model were adopted in this experiment.(1)Rats were assigned to normal control group(NC),diabetic control group(DC),diabetic metformin(DM),diabetic exercise group(DS)and metformin+exercise group(DMS).Rats were treated with metformin and aerobic exercise for 8weeks.Relevant indicators such as glycolipid metabolism,morphology of vascular,vascular inflammatory markers and oxidative stress were measured by methods of HE,ELISA,Western Blot and qPCR after intervention for 8weeks.The effect of aerobic exercise and metformin on vascular inflammation in diabetic rats are compared.(2)The protein and mRN A express of of NF-κBp65、IK Bα、SIRT1and Nampt of blood vessels in NC,DC and DS group after intervention for 8weeks were mesured by the methods of Western Blot and qPCR.The effect of aerobic exercise on SIRT1 and NF-κB of blood vessels in diabetic rats was discussed.(3)Rats were assigned to normal control group(NC),diabetic control group(DC),diabetic exercise group(DS),diabetic resveratrol group(SIRT1 agonist,DR),diabetic resveratrol+exercise group(DRS),diabetic PDTC group(NF-κB inhibitor,DP)and diabetic PDTC group+exercise(DPS).Rats were treated with medicant and exercise for 8 weeks.Relevant indicators such as glycolipid metabolism,morphology of vascular,vascular inflammatory markers and oxidative stress were measured by methods of HE,ELISA,Western Blot and qPCR after intervention.The mechanism in effect of aerobic exercise on vascular inflammation in diabetic rats was explored.Results:(1)Aerobic exercise,metfoimin and combination of aerobic exercise and metformin could reduce the level of FBG and FINS.(2)The levels of IL-1βTNF-α,MCP-1 and VCAM-1 were significantly reduced by Aerobic exercise.The level of VC AM-1 was significantly reduced by metformin.Combination of exercise and metformin could reduce significantly TNF-α,MCP-1,VCAM-1 and its express of mRNA,and increase the level of IL-10.Three methods can alleviate the injury of vascular endothelium.(3)Aerobic exercise,metformin and combination of aerobic exercise and metformin could reduce significantly reduce the protein express of NOX4,and increase the express of Nrf2 and HO-1.Aerobic exercise can reduce the mRNA express of NOX4,and increase SOD.Metformin can reduce MDA.Combination of exercise and metformin can reduce the mRNA express of NOX4 and MDA,increase the concentration of SOD and T-AOC.(4)Aerobic exercise can down-regluate the protein and mRNA express of NF-K b in diabetic rats and up-reglate the protein express of Ik Ba.Aerobic exercise can increase the express of SIRT1 and Nampt of protein and mRNA.(5)SIRT1 agonist and NF-k B can significantly improve blood glucose balance and insulin resistanc in diabetic rats,and alleviate vascular injury,and reduce the concentration of IL-1β and VCAM-1.Diabetic rats treated with SIRT1 agonist and NF-K B inhibitor showed lower levels of IL-1β and VCAM-1 compared with exercise.(6)SIRT1 agonist can significantly reduce the protein express of NOX4,and increase the protein express of Nrf2 and HO-1.NF-K B inhibitor can significantly reduce the protein express of NOX4,and increase the express HO-1 and SERUM concentration of T-AOC.The level of SOD was higher in diabetic rats treated both of SIRT1 agonist and exercise than it in those treated with exercise.The protein express of NOX4 and Nrf2 were reduced significantly in diabetic rats treated both of NF-K B inhibitor and exercise than them in those treated with exercise.(7)SIRTI agonist can increase significantly the protein express of IκB of blood vessels in diabetic rats.The protein express of IκBa in rats treated with both of SIRT1 agonist and exercise was increased significantly compared with rats treated with exercise.Conclusions:(1)Both of aerobic exercise and metformin can effectively relieve vascular inflammation in diabetic rats.Treatment effect in diabetic rats treated wih aerobic exercise and treated with exercise and metformin is better than it in rats treated with metformin.(2)Aerobic exercise and metformin alleviated vascular inflammation of diabetic rats partly by improving glucose metabolization and insulin and reducing oxidative stress of blood vessels.(3)Aerobic exercise may up-regulate the protein express of SIRT1 and Nampt of blood vessels in diabetic rats,and inhibit NF-κB signal.(4)Aerobic exercise may partly improve vascular inflammation in diabetic rats through SIRT1/NF-κB signaling pathway.