| Objective:To explore the effects of Astragaloside Ⅳ on endoplasmic reticulum stress in diabetic nephropathy based on the expression of inositol Requiring Enzyme1α and Glucose-Regulated Protein78 in renal tissue of rats Methods:Forty healthy male SD rats were randomly divided into normal control group(n =10)and model group(n = 30).Streptozotocin(STZ)was given to rats in the model group through intraperitoneal injection to establish DN model(random blood glucose ≥16.7mmol/L,24-hour urinary protein>30mg after 2 weeks as successful model).After successful modeling,the rats in the model group were randomly divided into Astragaloside group(n = 10),diabetic nephropathy group(n = 10)and resveratrol group(n = 10).Astragaloside group was given Astragaloside Ⅳ(40mg/kg),resveratrol group was given resveratrol(20mg/kg)while the diabetic nephropathy group and normal control group were provided with equal amount of distilled water per day for 8 weeks.During the course of the study,the general condition of rats was recorded,and blood glucose and body weight were measured regularly.The urine of rats in each group was collected at the end of 0 week,4 weeks and 8 weeks,and the quantity of 24-hour urinary protein and the concentration of urinary microalbumin were determined.At the end of the8 th week,blood was collected from the abdominal aorta and bilateral renal tissues were taken to measure the biochemical indexes such as serum creatinine(Scr),urea nitrogen(BUN),cholesterol(TC)and triglyceride(TG).The pathological changes of renal tissue were observed by HE staining and PASM staining,and the expressions of GRP78 and IRE-1 α in each group were detected and compared by immunohistochemical technique.Results:(1)Rats in the diabetic nephropathy group showed substantially worsen general condition than that in the normal control group,showing different degrees of mental burnout,dull hair color and depilation,in the mean time they exhibit phenomenon of increase in diet,drinking water,polyuria and weight loss.At the end of the 8th week,the general condition of the treated rats in the Astragaloside group and resveratrol group was better than that in the diabetic nephropathy group.(2)Compared with the normal group,at the end of 4th and 8th weeks,the body weight of the diabetic nephropathy group showed a significantly decrease and the blood glucose level was clearly elevated,while the Astragaloside group and resveratrol group showed a rather higher body weight and lower blood glucose level than that of the diabetic nephropathy group at the end of 4 and 8 weeks.(3)Compared with the normal group,the levels of blood urea nitrogen,serum creatinine,cholesterol,triglyceride,urinary microalbumin and 24-hour urinary protein in diabetic nephropathy group presented obviously increase than those in normal group(P<0.05).Compared with diabetic nephropathy group,the levels of Scr,BUN,TG,urinary microalbumin and 24-hour urinary protein in Astragaloside group and resveratrol group decreased at the end of the 8th week yet there was no meaningful difference in TC level of Astragaloside group.(4)Compared with the normal group,the diabetic nephropathy group presented with worse pathological results of renal tissue including increased mesangial matrix as well as narrowed renal tubule lumen and narrowed in epithelial cells,in correspondence with the immunohistochemical results that the expression of IRE1α and GRP78 increased.Compared with diabetic nephropathy group,the renal pathological damage in Astragaloside group and resveratrol group was minored and the expression of IRE1 α and GRP78 was decreased.Conclusion:Astragaloside Ⅳ plays a protective role in diabetic nephropathy by improving the endoplasmic reticulum stress of renal tissue in diabetic nephropathy rats. |
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