| Objective:Constructing the type 2 diabetic rats model. After the intervention of Angiotensin(1-7), observe the rat islet morphology and function, the expression of the serum angiotensin Ⅱ(angiotensinⅡ, Ang Ⅱ), the change of protein and gene of the transforming growth factor beta 1(TGF- beta 1), smad3, and Collagen I(Collagen Ⅰ) in islet tissue.Discuss the influence and mechanism of Ang-(1-7) on type 2 diabetes rat islet local fibrosis, in order to providing a new method to improve islet fibrosis of type 2 diabetes.Methods:36 healthy male Wistar rats,aged 8 weeks, were feed by standard laboratory diet for 2weeks, 12 of them were randomly selected as normal control(NC) group, be given normal diet. The remaining 24 were feed with high-fat and high-calorie diet, after 8 weeks,Through injecting of STZ(30 mg/Kg) to construct the type 2 diabetic rats model, a total of20 were builded successful, which were randomly divided into diabetes control group(DM,n=10) and Ang-(1-7) intervention groups [Ang-(1-7),n=10]. Ang-(1-7) group were intervention with Ang-(1-7) which dose was 300μg / ? kg-1 ? d-1 for eight weeks, DM group were given by the same dose of physiological saline. After the intervention of each rat, body weight, blood glucose, serum insulin, angiotensin Ⅱ(Ang Ⅱ) and steady state model of insulin resistance index(Homa IR) were tested. Using immunohistochemical staining method to examine local islet’s TGF-β1, smad3 and Collagen-Ⅰ protein expression, and using colored pathological image analysis system for quantitative analysis the results, at the same time,using HE staining to observe the each rat islet tissue’smorphology. Real-time(RT) PCR method was used to detect the expression level of TGF-β1, smad3 and Collagen-Ⅰ m RNA.Results:DM group compared to the NC group: In DM group,the weight was decreased obviously, the blood glucose, serum Ang Ⅱ levels, and Homa IR were significantly increased, while the serum insulin secretion were decreased(P < 0.05); In DM group, the expression of TGF-β1, smad3 and Collagen-Ⅰprotein in islet were increased to 3.07 times,2.21 times and 2.09 times compared with NC group, while the m RNA expression increased to 3.06 times, 2.81 times and 3.71 times, and the differences were statistically significant(P < 0.05); HE staining shows that in DM group, the number of rat islet was decreased, the structure was damaged, and the islet cells were atrophy, reduced, disordered arrangement.After the intervention of Ang-(1-7) compared with DM group: the structure damaged of islet was alleviated, the number of islet cell was increased, but not restored to the normal level; In two groups, except the weight of rats have no obvious changes, the blood glucose,serum Ang Ⅱ levels and Homa-IR were all reduced, serum insulin secretion was increased(P < 0.05); In Ang-(1-7) group, the expression of TGF-β1, smad3 and Collagen-Ⅰprotein in islet were reduced to 67.39%, 78.57% and 73.91% compared with NC group, while the m RNA expression reduced to 50.31%, 67.45% and 54.68%, and the differences were statistically significant(P < 0.05).Conclusions:Ang-(1-7) can significantly improve the morphology, function and fibrosis of the type 2 diabetes rat islet, and its mechanism may be through down-regulation the signal transduction pathways of TGF-β1/smads, improve the insulin resistance, increase the secretion of pancreatic islet beta cell function. |
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