Effects Of Ang-(1-7) On Inflammatory Pathway Of IKKβ/NF-κB In Hepatic Tissus Of Diabetes Mellitus Rats

Objective:In this study we established rats model of diabetes mellitus induced by STZ,to observe the peptide angiotensin(1-7)[Ang-(1-7)] effect on the morphology of liver tissue of rats,and the effect on the key inflammatory pathway and inflammatory factor,explore the anti-inflammatory mechanism,to improve the new diabetes mellitus ideas and targets.Methods:Experiment 34 healthy male Wistar rats aged 8 weeks,1 weeks after normal diet fed,10 rats were selected as normal control group(NC),fed with normal diet;the remaining 24 is with high fat and high calorie diet.After 8 weeks of feeding with small dose of STZ(30mg/Kg)at a time intraperitoneal injection of construct DM rat model,the successful model of a total of 20.Randomly divided into 2 groups: diabetes mellitus group(DM group,n=10)and Ang-(1-7)intervention group(group DA,n=10),Ang-(1-7)intervention group(group DA)to Ang-(1-7)(300μg·kg– 1·d– 1)subcutaneous injection,NC group and D0 group given the same volume of saline was injected into the subcutaneous neck,a total of 8 weeks of intervention.The weight of rats in each group were measured after the end of the intervention,fasting blood glucose,serum insulin and angiotensin II(Ang II)content,the calculation of HOMA-IR and HOMA-ISI;HE to compare the liver pathological structure of each group of rats,immunohistochemistry method was used to detect the level of IKKβ and NF-κB protein in the liver,and the expression of IKKβ,NF-κB,TNF-alpha,IL-6 gene was detected by real-time fluorescence quantitative(RT).Result:Compared with NC group,DM group rats weight,fasting blood glucose,serum Ang and Homa-IR increased,insulin levels decreased,and there were statistically significant differences(P < 0.05);liver lobules,fuzzy disorders,liver cell necrosis,which has different degrees of punctate or focally infiltration of inflammatory cells.Fat deposition significantly increased 72.6%;HOMA-IR(P<0.05),HOMA-ISI decreased by 18.4%(P<0.05);liver tissue IKKβ,NF-κB protein levels were increased by 1.13 times,1.07 times,The expression levels of IKKβ,NF-κB,TNF-α,IL-6 m RNA levels were increased by 3.27,2.96,5.16,5.19 times.The differences were statistically significant(P<0.05);Ang-(1-7)DM rats after treatment,fasting blood glucose,Ang decreased significantly(P<0.05);fasting insulin increased significantly(P<0.05);HOMA-IR(P<0.05),reduced by 15.1%HOMA-ISI increased 4.8%(P<0.05);clear liver small leaf contour,liver cell fat deposition in improved liver cell necrosis and inflammatory cell infiltration was less,weight gain was not statistically significant.The expression levels of IKKβ,NF-κB protein in liver tissue were 37.09% and 32.17%,respectively.The expression levels of IKKβ,NF-κB,TNF-α,IL-6 RNA were decreased by 50.53%,35.35%,and 34.69%,respectively,and the differences were statistically significant(P<0.05).Conclusions: In diabetic rats after Ang-(1-7)intervention could increase ACE2-Ang(1-7)-Mas pathway activity,improve hepatic inflammation,liver expression of inflammatory pathways,reduce liver inflammatory factors in diabetic rats,improve hepatic glucose metabolism,thereby reducing insulin resistance,increase liver glycogen synthesis,reduce blood sugar that has insulin sensitizing effect.