Dapagliflozin Attenuates Renal Lesion by Inhibiting NLRP3 Inflammasome in Diabetic Rats
Objective:To investigate the effect of dapagliflozin on renal injury in diabetic rats and its molecular mechanism.Methods:Diabetic rat model was established by high fat diet combined with intraperitoneal injection of small dose streptozotocin(STZ).The diabetic model rats were randomly divided into control group,model group,metformin(Met)group and dapagliflozin(DAPA)group.The rats in the Met group and DAPA group were given intragastric administration of Met(150 mg/kg per day)and DAPA(10 mg/kg per day)respectively,while the rats in the control group and model group were given equal volume of distilled wa-ter,once a day for 6 weeks.The rats were weighed once a week to adjust the dosage according to the change of body weight.After medication for 6 weeks,fasting blood glucose(FBG),serum triglyceride(TG),serum total cholesterol(TC),24 h urinary albumin(UTP)and urinary albumin/creatinine ratio(ACR)were measured.Hematoxylin eosin(HE)staining,as well as periodic acid-schiff(PAS)staining and Masson's trichrome staining(Masson)was used to detect the pathological changes of renal tissue.The pro-tein expression of NLRP3,caspase1,IL-1β and IL-18 in renal tissue of rats in each group was detected by Western blot and im-munohistochemistry.Results:There were significant differences in FBG,TG,TC,UTP,ACR and SGLT2 protein expression levels between model group and control group(P<0.01),and the pathological changes of model group were significant.Compared with the model group,the levels of TC,TG,ACR,FBG and UTP in the rats of DAPA group decreased,the protein expression of NLRP3,caspase-1,IL-1β and IL-18 in renal tissues were decreased(P<0.05,P<0.01);the levels of TC,TG and FBG in the rats of Met group decreased,the protein expression of NLRP3,IL-1β and IL-18 in renal tissues were also decreased(P<0.05,P<0.01).Met and DAPA treatment improved renal pathological changes in diabetic rats.Conclusion:Dapagliflozin can exert renal pro-tective function by inhibiting NLRP3 inflammasome and its downstream inflammatory factors in diabetic rats.
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万方数据
维普
