| Objective:To study the effect of Astragaloside Ⅳ(AS-Ⅳ)on the expression of GSDMD and caspase-1 in kidney of diabetic nephropathy(DN)rats.Methods:Methods:Thirty SD male rats were randomly selected from 40 healthy SD rats to establish diabetic nephropathy rat model by intritoneal injection of Streptozotocin(STZ)(blood glucose is higher than 16.7mmol/L three days later,24 h urinary albumin excretion >30mg/d two weeks later to determine the success of diabetic nephropathy mouse model).Then they were randomly divided into 3 groups,10 in each group: diabetic nephropathy group(DN group),Astragaloside Ⅳ intervention group(AS-Ⅳ group)and resveratrol group.The remaining 10 were normal control group(NC group).AS-Ⅳ group was gavaged daily(40mg/kg),resveratrol group was gavaged daily(20mg/kg),DN and NC groups were given the same dose of distilled water gavage.The rats’ body weight,blood glucose and urinary microalbumin were measured at week 0,week 4 and week 8,respectively.Bilateral kidney tissues were collected through abdominal aorta at week8,and biochemical indexes such as serum creatinine,urea nitrogen,cholesterol,triglyceride were measured.The histomorphological changes of kidney were observed by HE staining.The expression of Caspase-1 and GSDMD was detected by immunohistochemistry.Results:(1)The normal group showed no yellowing of hair color and shedding,and the activity was good.The DN group showed obvious emaciation,listless spirit,high intake of food,water and urine,yellow hair and shedding.At the end of 8 weeks,the above conditions of the AS-Ⅳ group and resveratrol group were better than those of the DN group.(2)At the 4th and 8th week of the experiment,it was found that the weight of rats in DN group was lower than that in NC group,and the weight of rats treated with ASⅣ and resveratrol increased(P<0.05),but lower than that in NC group.(3)Compared with NC group,blood glucose in DN group was significantly increased(P<0.05);The blood glucose level of AS-Ⅳ and resveratrol treated rats was monitored at the end of the 4th week,and no significant change was found in blood glucose compared with DN group(P>0.05),at the end of the 8th week,the blood glucose of rats treated with AS-Ⅳ and resveratrol was still higher than that of NC group(P<0.05),but decreased compared with DN group;Results were similar between the AS-Ⅳ group and the resveratrol group(P>0.05).(4)Compared with NC group,urinary microalbumin,BUN,Scr,TG and TC in DN group were significantly increased(P<0.05);Compared with DN group,urine microalbumin,BUN and Scr were decreased in AS-Ⅳ and resveratrol treated rats(P<0.05);There was no significant change in TC in AS-Ⅳ treated rats compared with DN group(P>0.05),TG level decreased(P<0.05);The levels of TG and TC in resveratrol treated rats decreased(P<0.05).(5)Compared with the normal group,at the end of 8 weeks,DN rats showed different degrees of renal lesions: hyperplasia,thickening of basement membrane and widening of mesangium,vacuolar degeneration and dilation of renal tubules,immunohistochemical results suggested increased expression of Caspase-1 and GSDMD(P<0.05);Compared with DN group,AS-Ⅳ group and resveratrol group had less renal lesion,and the expression of Caspase-1 and GSDMD decreased(P<0.05).Conclusion:AS-Ⅳ may improve cell death and delay the progress of DN by down-regulating the expression of GSDMD and Caspase-1 in renal tissue of DN rats. |
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