The Effects Of Autophagy In The Diabetic Rats With Contrast-Induced Acute Kidney Injury Via The Intervention Of Atorvastatin

Objective:To investigate the expression of autophagy and apoptosis in the contrast-induced acute kidney injury with the atorvastatin intervention and to explore the relationship between them in vivo。Methods:Diabetic rats model was established with Abdominal urea with a single dose injection of streptozotocin。Raising eight weeks and then diabetic rats were randomly divided into 8 groups: blank control group(N group),diabetes control group(DM group),diabetes+contrast media group(DM+CM group),diabetes+ contrast media+3-MA group(DM+CM+3-MA group),diabetes+contrast media+5 mg/kg/d atorvastatin group(ATO1 group),diabetes+contrast media+10 mg/kg/d atorvastatin group(ATO2 group), diabetes+contrast media+30 mg/kg/d atorvastatin group(ATO3 group),diabetes+3-MA+contrast media+30 mg/kg/d atorvastatin group(DM+CM+3-MA+ATO3 group),injection of Iodinated contrast media after 24 h to collect the urine specimen with metabolic cages to test the urine creatinine(Ucr))and 24 hours urine albumin(24h-Ualb),and record the 24 h urine and 24 hours urinary albumin excretory(24h-UAE)。Injection of Iodinated contrast media after 48 h to collect the blood specimen to detect the serum creatinine(Scr)and blood urea nitrogen(BUN),and calculate the endogenous creatinine clearance rate(Ccr)。Executed the rats to obtain the left kidney tissue for pathology analysis,TUNEL to detect apoptosis and immune histochemical method to detect the protein expression of Caspase3,Lc3,Bcl-2 in renal medulla。To obtain the right kidney to use the Western Blot method(Western Blot) to detect the protein expression of Lc3 and Beclin1 in renal medulla。Results:1.Compared with the N group,the autophagy level of the DM group was increased;Instead of,the autophagy level of the DM+CM group was lower than the DM group;the autophagy level of the DM+CM+3-MA group was obviously less than DM+CM group;Compared with the DM+CM group,the autophagy level of the ATO(1、2、3) group were increased significantly;Compared with the DM+CM+3-MA group,the autophagy level of the DM+CM+3-MA+ATO3 group was increased,but still lower than ATO3 group。2.Compared with the DM group,the apoptosis level of DM+CM group was obviously increased and the DM+CM+3-MA group was increased more obviously;compared with the DM + CM group,the apoptosis level of ATO(group 1、2、3)were decreased obviously;Compared with DM+CM+3-MA group, the apoptosis level of the DM+CM+3-MA+ATO3 group was lower,but still higher than ATO3 group。3.In a word,within a certain limits,the level of autophagy was increased in resistance to the level of apoptosis,and beyond a certain limits,the level of autophagy would’t to resist the level of apoptosis。To inhibit the level of autophagy via the 3-MA could increase the level of apoptosis,and by the intervention of ATO,the level of autophagy was increasing instead of the level of apoptosis was reducing。Conclusion:Iodinated contrast media can induce the level of apoptosis in renal tubular epithelial cells in diabetic rats,and in the early process of apoptosis,the level of autophagy was increased to resist the level of apoptosis。If the damage beyond a certain limits,the level of autophagy is not enough to resist the level of apoptosis。The atorvastatin can resist the effects of Iodinated contrast media,and this function may be related to enhance the effects of autophagy。...