Protective Effects And Mechanism Of Edaravone On Acute Kidney Injury Induced By Sepsis

Part Ⅰ Protective effects of edaravone on septic Acute kidney injuryObjective This study was designed to investigate the renal changes in rats with sepsis and the effects of edaravone on renal faction, expression of inflammatory factor, renal pathological changes,injury of renal mitochondrial ultrastructure, and to discuss the protection of edaravone on septic acute kidney injury.Methods In a modeal of rats in which LPS was injected intraperitoneallly,144SD rats were randomly divided into control(control group, n=36), LPS(LPS group, n=36), LPS+EDA (LPS+EDA group, n=36) groups. At3h,6h,12h after septic rats had been induced, each groups(12rats every time)were executed and their renal tissue and serum were collected respectively to detect blood urea nitrogen and serum creatinine, TNF-α and IL-6, IL-10by enzyme-linked immunosorbent assay(ELISA), the changes of renal pathology and renal mitochondrial ultrastructure. slides both light microscope and electron microscope were Scored. Results Compared with control group, in LPS group, the urea nitrogen and serum creatinine increasedand peaked at12hours points(P<0.05), The level of TNF-a, IL-6peaked at3hours points, decreased at6hours points. IL-10peaked at6hours points, and decreased at12hours points(P<0.05), obvious pathological and mitochondrial ultrastructure changes existed(P<0.05). Edaravone significantly decreased urea nitrogen and creatinine, level of TNF-a and IL-6.The histological changes of renal injury were ameliorated in LPS+EDA group. The changes of mitochondrial mitochondrial ultrastructure were ameliorated also. There were no significant difference between control group and EDA group.Conclusion This study showed that edaravone administered inhibit of TNF-a and IL-6, and provided protective effects on the kidney against acute injury induced by sepsis. Part Ⅱ Protective effects of edaravone on mitochondria in septic acute kidney injuryObjective To investigate the effects of edaravone on renal mitochondrial membrane potential and oxidative stress indices and possible mechanism of edaravone protect against acute kidney injury induced by sepsis.Methods In a modeal of rats in which LPS was injected intraperitoneallly,144SD rats were randomly divided into control(control group,n=36), LPS(LPS group n=36), LPS+EDA(LPS+EDA group n=36) groups. At3h,6h,12h after septic rats had been induced, each groups(12rats every time)were executed and their renal tissue were collected. Mitochondria were extracted from renal tissue to detect mitochondrial membrane potential and T-AOC, SOD, GSH, CAT, MDA, NO, TNOS, iNOS.Result Compared with in control group, in LPS group renal mitochondrial membrane potential(P<0.05), T-AOC was lower(P<0.05); the activity of SOD,CAT was lower at6,12hours points(P<0.05); The content of GSE、NO was lower,but the content of MDA and the activity of T-NOS, iNOS was obvious higher(P<0.05). Edaravone improve mitochondrial membrane potential, and the activity of antioxidase, inhibited T-NOS, iNOS. The T-AOC in EDA group was obviously higher than in control group(P<0.05), and there were significant difference between the two groups in other indices(P>0.05).Conclusion Edaravone improved mitochondrial membrane potential, inhibited oxidative stress, and protect renal mitochondria. PartⅢ Protective effects of edaravone on apoptosis in septic acute kidney injuryObjective To investigate the effects of edaravone on apoptosis and expression level of cytochrome C, Caspase-3of kidney in rats model of sepsis.Methods In a modeal of rats in which LPS was injected intraperitoneallly,144SD rats were randomly divided into control(control group,n=36), LPS(LPS group n=36), LPS+EDA(LPS+EDA group n=36) groups. At3h,6h,12h after septic rats had been induced, each groups(12rats every time) were executed and their renal tissue were collected. Apoptosis index was detected by TUNEL assay. Expression level of cytochrome C, Caspase-3was measured by Western Blot method.Result The number of apoptotic cells in LPS group increased, and expression level of cytochrome C, Caspase-3was increasing also. Edaravone can reduced the number of apoptotic cells, inhibited expression level of cytochrome C, Caspase-3.Conclusion Edaravone can inhibited renal cells apoptosis though mitochondrial way.