Effection And Mechanism Of Losartan On Islet Tissue Of Diabetic Rats

ObjectiveTo investigate the effect of Losartan which is the receptor blockers of Angiotensin II on expression of TGF-β1, Smad7and Collagen I in islet tissue of diabetic rats,so that we can try to prove the effect of Losartan on islet tissue fibrosis of diabetic rats. The method of immunohistochemical, HE staining and PCR were used.Islet tissue fibrosis of diabetic rats were discussed from protein-level and gene-level when the rats were intervened with Losartan,in order to offer the new thinking about the research on islet tissue fibrosis of diabetic rats.Methods26adult Wistar rats that were healthy were regarded as experimental subject,in which random8rats were choosed as Normal control group, which were fed with normal diet, the other18rats were fed with high fat and high sugar diet. After eight weeks the other18rats were injected of streptozotocin to induced diabetic rats.16rats were induced successfully,which were divided into diabetes group and Losartan group. Losartan-intervened group were gavaged with Losartan30mg/kg/d. After8weeks,Glucose, insulin, weight and insulin resistance index were observed.Then execute all the groups and take out islet tissue. The level of TGF-β1, Smad7and Collagen I protein in pancreatic tissue were examined by immunohistochemistry and were quantitatively analyzed by color pathological image analysis system.HE staining was used to observe shape of islet tissue.The level of TGF-β1, Smad7and Collagen I mRNA in islet tissue were examined by PCR. Results1.Compared to normal control group, insulin and weight were significantly decreased in diabetic rats group, blood glucose and insulin resistance index were significantly increased (P<0.05).There were Significant improvements in every index except weight (P<0.05)2.Immunohistochemistry:Indicators In normal group were TGF-131(0.16±0.05),smad7(0.39±0.05),Collagen I (0.29±0.08).In diabetes group,the level of TGF-β1(0.44±0.09)protein and Collagen I (0.45±0.05)protein in islet tissue were expressed significant increasingly,Smad7(0.20±0.06)protein reduced (P <0.05).Losartan administration made all changes much better,TGF-β1(0.31±0.10),smad7(0.33±0.07),Collagen I (0.34±0.06).(P<0.05). Intergroup comparisons were statistically significant (P<0.05).3HE staining:under the light microscope,pancreatic tissue of normal control group was normal,but shape of pancreatic tissue in diabetes group was disorganized,and Fiber and connective tissues increased in amount.Compared with diabetes group, lesion of islet tissue in Losartan-intervened group was alleviated,but not restored to the normal level.4. Real-time PCR:Indicators In normal group were TGF-β1(1.58±0.04),smad7(2.91±0.14),Collagen I (1.57±0.04).In diabetes group,the level of TGF-β1(4.97±0.12)mRNA and Collagen I (5.99±0.11)mRNA in islet tissue were expressed significant increasingly,Smad7(1.16±0.01) mRNA reduced (P <0.05).Losartan administration made all changes much better, TGF-β1(2.42±0.06,smad7(2.03±0.09),Collagen I (3.38±0.19)(P<0.05). Intergroup comparisons were statistically significant (P<0.05).Conclusion1.Occurrence and development of islet tissue fibrosis in diabetic rats is related to signal transduction pathways of TGF-β1/smads. 2. Losartan can improve islet tissue fibrosis and protect function of islands of langerhans.3.Improving of Losartan in islet tissue fibrosis of diabetic rats may be related to TGF-β1down-regulation and smad7up-regulation in signal transduction pathways of TGF-β1/smads, reduceing the level of Collagen I...