RESEARCH ON EFFECT OF AGEs-RAGE SIGNALING PATHWAY ON MYOCARDIAL FIBROSIS OF TYPE TWO DIABETIC RATS A

来源 :2014年广州运动与健康国际学术研讨会 | 被引量 : 0次 | 上传用户:zzhijian
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  Diabetic cardiomyopathy (DCM) is one of the chronic complications of diabetes mellitus (DM), and it is one of the main reasons of DM deaths.Some studies showed that DCM always comes along with fibroblast proliferation, much collagen synthesis and myocardial collagen deposition, which will lead to cardiac hypertrophy, heart function damage and heart failure.So myocardial fibrosis has become a hot study topic of DM complications in recent years.The pathogenesis of DCM has many reasons, but advanced glycation end products (AGEs) which as the products of chronic hyperglycemia and oxidative stress has become a central position of DCMstudy.In this research, the type 2 diabetic rats were successfully established through intraperitoneal injecting a low-dose streptozotocin-treated (STZ, 30mg/kg) to SD rats that had been fed high-fat fodder for six weeks, and the research discussed the effect of AGEs/RAGE signaling pathway on myocardial fibrosis of type 2 diabetic rats after 12-week swimming and oral EGCG.The type 2 diabetic rats had demonstrated myocardial fibrosis in the 12th week after the rats model successfully established.With the further development of type 2 diabetes, myocardial fibrosis, myocardial AGEs contents and RAGEprotein expression of the type 2 diabetic rats were gradual increasing.12-week swimming or/and oral EGCG could reduce the level of myocardial Hyp content, CVFand Col I, Col Ⅳ, FNexpression in myocardium of type 2 diabetic rats to a different extent, and the degree of reduction with two interventions was greater than the single intervention.The signaling pathway of AGEs/RAGE/oxidative stress/NF-κ B plays an important role in myocardial fibrosis of DM.12-week swimming or/and oral EGCG could improve the signaling pathway of AGEs/RAGE/oxidative stress/NF-κ B in myocardium of type 2 diabetic rats to a different extent, and the degree of improvement with two interventions was better than the single intervention.TGF-β/Smads is an important signaling pathway which leads to fibrosis.The signaling pathway of AGEs/RAGE/oxidative stress/NF-κ B has a direct or indirect activation of TGF-β/Smads signaling pathway.12-week swimming or/and oral EGCG could inhibit TGF-β/Smads signaling pathway which through reducing Smad2mRNA, TGF-β1 and CTGF protein expression, and increasing Smad7mRNA expression in myocardium of type 2 diabetic rats to a different extent, and the degree of inhibition with two interventions was greater than the single intervention.The AGEs/RAGE signaling pathway plays an important role in myocardial fibrosis of type 2 diabetes.The research showed that 12-week swimming or/and oral EGCG could improve myocardial fibrosis of type 2 diabetic rats by reducing myocardial AGEs contents and inhibiting AGEs/RAGE downstream signaling pathways to a different extent.The signaling pathway of AGEs/RAGE may be one new target in the mechanisms of exercise and medicine treating myocardial fibrosis of type 2 diabetes.
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