| Objective:To test the level of angiotensin 1-7(Ang 1-7)in patients with different levels of glucose,to test the renal injury during diabetes and to examine the effectiveness of Ang 1-7 on endoplasmic reticulum(ER)stress in the kidney of diabetic rats.Methods:Ninety-five subjects without diagnosed diabetes were screened in the Tianjin Seaside People's Hospital in the December 2014.Type 2 diabetes diagnostic criteria: fasting blood glucose ? 7.0mmol/L,postprandial blood glucose ? 11.1mmol/L with reference to the Chinese type 2 diabetes prevention guide in 2010.Patients diagonized with impaired glucose tolerance impaired fasting glucose between 6.1 and 7.0 mmol/L and impaired postprandial glucose regulation 7.8 to 11.1 mmol/L for 2h postprandial glucose.Oral glucose tolerance test was implemented.Subjects were divided into three groups including normal group(n=31),impaired glucose group(n=32),and diabetes group(n=32)ralated to the level of blood glucose.Body weight,waist circumference,blood pressure,renal function,liver function,blood lipids,Ang 1-7,angiotensin-converting enzyme(ACE)2 and other indicators were detected.The levels of Ang 1-7 and the relationship with blood glucose were evaluated.Further non-conditional Logistic regression to explore the influencing factors for blood glucose.Twenty healthy male Sprague-Dawley rats(150-200g)were chosen.Of those,fifteen rats were randomly selected and fed with high-fat diet.The remaining five rats were fed with normal diet.According to the random number method,eight weeks later,15 high-fat-fed rats were fasted for 12 hours(overnight fasting,no water)and were prepared as diabetic rat model through intraperitoneal injection of streptozotocin.Five rats were injected with citric acid buffer as the control group.Eleven of them were diagonized with type 2 diabetes mellitus,three died and one was failed to be modeled.Rats with diabetes were randomly divided into two groups.One group was given intervention of Ang 1-7(576 ng/d)with drug pump,named Ang 1-7 group with 5 rats.The remain rats were pumped into the same volume of normal saline as the diabetic group with 6 rats.Five healthy SD rats were in the control group.All rats were sacrificed after intervention for two weeks.Blood samples were collected to test serum creatinine.Urine samples were examined for 24-hour urinary protein.Kidney specimens were used to test the level of ER stress proteins,including chaperone glucose-regulated protein(GRP)78,activity of transcription factor(ATF)4,enhancer binding protein homologous protein(CHOP)levels,by Western Blot and Real-time Quantitative PCR.Apoptosis in renal tissue were tested by western blot and immunohistochemistry.Results:There were significant difference in triglycerides,ACE2,Ang 1-7 among the three groups and statistical difference was found between diabetes group(TG: 3.4 ± 0.9,ACE2: 28.6 ± 4.7,Ang 1-7: 14.4 ± 4.2)and impaired glucose group(TG1.5 ± 0.8,ACE2: 21.8 ± 4.2,Ang 1-7: 11.0 ± 3.5)(p <0.017).Further non-conditional Logistic regression showed that ACE2 and Ang 1-7 were the risk factors for blood glucose.Levels of protein in GRP78,ATF4,and CHOP increased significantly in diabetic rats compared to normal rats(F=6.46,p<0.05).Ang 1-7 infusion could reduce the levels of GRP78,ATF4,and CHOP significantly compared to diabetic rats(F=5.82,p<0.05).The expression of caspase 3 in Ang 1-7 group was significantly lower than that in diabetic group by western blot and immunohistochemistry.Conclusion:Angiotensin1-7 level was increasing in patients with newly diagnosed diabetes..Ang 1-7 could reduce ER stress and apoptosis in the kidney of diabetic rats. |
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