The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury(IRI) in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for ...The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury(IRI) in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for 60 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups: sham-operated group(sham), IRI+saline group(IRI group), IRI+Fenofibrate(FEN) group. Normal saline or Fenofibrate(3 mg/kg) was intravenously injected 60 min before renal ischemia in IRI group and FEN group, respectively. Blood samples and renal tissues were collected at the end of reperfusion. The renal function, histopathologic changes, and the expression levels of pro-inflammatory cytokines [interleukin-8(IL-8), tumor necrosis factor alpha(TNF-α) and IL-6] in serum and renal tissue homogenate were assessed. Moreover, the effects of Fenofibrate on activating phosphoinositide 3 kinase/protein kinase B(PI3K/Akt) signaling and peroxisome proliferator-activated receptor-α(PPAR-α) were also measured in renal IRI. The results showed that plasma levels of blood urea nitrogen and creatinine, histopathologic scores and the expression levels of TNF-α, IL-8 and IL-6 were significantly lower in FEN group than in IRI group. Moreover, Fenofibrate pretreatment could further induce PI3K/Akt signal pathway and PPAR-α activation following renal IRI. These findings indicated PPAR-α activation by Fenofibrate exerts protective effects on renal IRI in mice by suppressing inflammation via PI3K/Akt activation. Thus, Fenofibrate could be a novel therapeutic alternative in renal IRI.展开更多
AIM:To assess the hepatic changes after induction of different periods of renal ischemia. METHODS:Rats were subjected to either sham operation or ischemia (30,45 and 60 min) followed by 60 min reperfusion. Liver and r...AIM:To assess the hepatic changes after induction of different periods of renal ischemia. METHODS:Rats were subjected to either sham operation or ischemia (30,45 and 60 min) followed by 60 min reperfusion. Liver and renal functional indices were measured. Hepatic glutathione (GSH) and ferric reducing antioxidant power levels and the concentration of interleukin (IL)-10 and tumor necrosis factor (TNF-α) were evaluated. Portions of liver and kidney tissues were fixed for histological evaluation. RESULTS:Forty-five minutes renal ischemia followed by 60 min reperfusion caused significant changes in liver structure and a significant reduction in renalfunction. These rats showed a significant decrease in liver GSH,as well as a significant increase in TNF-α and IL-10 concentrations. These results demonstrated that renal ischemia caused changes in liver histology,function,oxidative stress and inflammatory status,which led to a reduction in hepatic antioxidant capacity. With 30 min ischemia,the magnitude of these changes was less than those with 45 or 60 min ischemia.CONCLUSION:A minimum of 45 min ischemia is needed to study the effects of renal injury on the liver as a remote organ.展开更多
Objective:To investigate glucose metabolic alterations in cerebral cortical subareas using ^(18)F-labeled glucose derivative fluorodeoxyglucose(FDG)micro-positron emission tomography(PET)scanning in a rat renal ischem...Objective:To investigate glucose metabolic alterations in cerebral cortical subareas using ^(18)F-labeled glucose derivative fluorodeoxyglucose(FDG)micro-positron emission tomography(PET)scanning in a rat renal ischemia/reperfusion(RIR)model.Methods:Small-animal PET imaging in vivo was performed with ^(18)F-labeled FDG as a PET tracer to identify glucose metabolic alterations in cerebral cortical subregions using a rat model of RIR.Results:We found that the average standardized uptake value(SUV_(average))of the cerebral cortical subareas in the RIR group was significantly increased compared to the sham group(P<0.05).We also found that glucose uptake in different cortical subregions including the left auditory cortex,right medial prefrontal cortex,right para cortex,left retrosplenial cortex,right retrosplenial cortex,and right visual cortex was significantly increased in the RIR group(P<0.05),but there was no significant difference in the SUV_(avcrage) of right auditory cortex,left medial prefrontal cortex,left para cortex,and left visual cortex between the two groups.Conclusion:The ^(18)F-FDG PET data suggests that RIR causes a profound shift in the metabolic machinery of cerebral cortex subregions.展开更多
Background:Peroxiredoxin-3(Prx-3)is known to be involved in the clearance of cellular hydrogen peroxide and plays an important role in protecting the myocardial tissue against damage of oxidative stress.However,the ro...Background:Peroxiredoxin-3(Prx-3)is known to be involved in the clearance of cellular hydrogen peroxide and plays an important role in protecting the myocardial tissue against damage of oxidative stress.However,the role of Prx-3 in protecting the myocardial tissue against renal ischemia/reperfusion(I/R)-induced myocardial injury(RI/RMI)remains unknown.We aimed to examine the antioxidative effect of Prx-3 using a rat RI/RMI model in an attempt to find a new approach to the prevention and treatment of myocardial injury induced by renal I/R.Methods:A RI/RMI rat model was established to detect the renal histopathology and renal functions by hematoxylin-eosin staining staining and commercially available assay kits.The myocardial antioxidant activity and the expressions of mRNA and protein of Prx-3 in the myocardial tissue were measured by real-time polymerase chain reaction and Western blotting assay,respectively.Results:Compared with the normal and control groups,the serum level of blood urea nitrogen and serum creatinine was significantly increased in the I/R group(P<0.05).Histopathological changes in the kidneys were also more obvious,including glomerular cystic and renal interstitial hemorrhage,renal tubular epithelial cell edema,and tubular type formation.The mRNA and protein expressions of Prx-3 were increased significantly in the RI/MRI rat model as compared with those in the normal and control groups.Conclusion:Oxidative damage occurred in the remote myocardium after renal I/R and Prx-3 was able to enhance the self-regulatory ability of the myocardium against damage from oxidative stress after RI/MRI.展开更多
Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were random...Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group,IRI group, empty plasmid group and AM group. One week after re-展开更多
Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue.Methods:Fourty eight rats were randomly divided into four groups(n=12):sham operation group,30 min ischemia 60 min reperfusion gr...Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue.Methods:Fourty eight rats were randomly divided into four groups(n=12):sham operation group,30 min ischemia 60 min reperfusion group,60 min ischemia 60 min reperfusion group,and120 min ischemia 60 min reperfusion group.The brain tissues were taken after the experiment.TUNEL assay was used to detect the brain cell apoptosis,and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemiareperiusion induced apoptosis of brain tissues,and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreased Bcl-2 expression,increased Bax expression,upreguiated expression of NF- κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage,manifested as induced brain tissues apoptosis and inflammation activation.展开更多
AIM To evaluale the potential role of P-selectinand anti-P-selectin monoclonal antibody(mAb)in apoptosis during hepatic/renal ischemia-reperfusion injury.METHODS Plasma P-selectin level,hepatic/renal P-selectin expres...AIM To evaluale the potential role of P-selectinand anti-P-selectin monoclonal antibody(mAb)in apoptosis during hepatic/renal ischemia-reperfusion injury.METHODS Plasma P-selectin level,hepatic/renal P-selectin expression and cell apoptosiswere detected in rat model of hepatic/ renalischemia-reperfusion injury.ELISA,immunohist-ochemistry and TUNEL were used.Someischemia-reperfusion rats were treated with anti-P-selectin mAb.RESULTS Hepatic/renal function insuffic-iency,up-regulated expression of P-selectin inplasma and hepatic/renal tissue,hepatic/renalhistopathological damages and cell apoptosiswere found in rats with hepatic/renal ischemia-reperfusion injury,while these changes becameless conspicuous in animals treated with anti-P-selectin mAb.CONCLUSION P-selectin might mediateneutrophil infiltration and cell apoptosis andcontribute to hepatic/renal ischemia-reperfusioninjury,anti-P-selectin mAb might be an efficientapproach for the prevention and treatment ofhepatic/renal ischemia-reperfusion injury.展开更多
Background Ascorbic acid has important antioxidant ischemic preconditioning on later ischemia-reperfusion ascorbic acid in ischemic preconditioning in the kidney. properties, and may play a role in the protective effe...Background Ascorbic acid has important antioxidant ischemic preconditioning on later ischemia-reperfusion ascorbic acid in ischemic preconditioning in the kidney. properties, and may play a role in the protective effects of Herein, we examined the role of endogenous extracellular Methods We developed a solitary rabbit kidney model where animals received ischemia-reperfusion only (ischemia-reperfusion group, n=-15) or ischemic preconditioning followed by ischemia-reperfusion (ischemic preconditioning group, n=15). Ischemia-reperfusion was induced by occluding and loosening of the renal pedicle. The process of ischemic preconditioning included 15-minute brief ischemia and 10-minute reperfusion. In vivo microdialysis coupled with online electrochemical detection was used to determine levels of endogenous extracellular ascorbic acid in both groups. The extent of tissue damage was determined in kidney sections stained with hematoxylin and eosin. Serum creatinine and urea nitrogen were also detected to assess renal function. Results During ischemia-reperfusion, the extracellular ascorbic acid concentration during ischemia increased rapidly to the peak level ((130.01±9.98)%), and then decreased slowly to near basal levels. Similar changes were observed during reperfusion (peak level, (126.78±18.24)%). In the ischemic preconditioning group there was a similar pattern of extracellular ascorbic acid concentration during ischemic preconditioning. However, the ascorbic acid level was significantly lower during the ischemia and early reperfusion stage compared to the ischemia-reperfusion group. Additionally, the extent of glomerular ischemic collapse, tubular dilation, tubular denudation, and loss of brush border were markedly attenuated in the ischemic preconditioning group. Levels of serum creatinine and urea nitrogen were also decreased significantly in the ischemic preconditioning group. Conclusions Ischemic preconditioning may protect renal tissue against ischemia-reperfusion injury via use of extracellular ascorbic acid. In vivo microdialysis coupled with online electrochemical detection is effective for continuous monitoring extracellular ascorbic acid in the renal cortex.展开更多
Objective: To examine the effect of warm and cold ischemia on functions of the operated kidney in cases with a normal contralateral kidney undergoing nephron sparing surgery. Methods: This study enrolled 40 patients w...Objective: To examine the effect of warm and cold ischemia on functions of the operated kidney in cases with a normal contralateral kidney undergoing nephron sparing surgery. Methods: This study enrolled 40 patients with a normal contralateral kidney and without a renal function threatening risk factor, who were operated with NSS. The patients were randomized at admission. They were divided into 2 equal groups as warm and cold ischemia. An ice application for 10 minutes was done to cold ischemia group after clamping renal artery. Renal functions were evaluated with Technesium-99m-Dimercaptosuccinic Acid (DMSA) and serum creatinine at the preoperative and postoperative (day 1, day 15, month 6, and month 12) period. Statistical analysis was done with Mann Whitney U test, Wilcoxon Signed Rank test, and Fredman test. A p value below 0.05 was considered statistically significant. Results: There were no significant differences between the groups in terms of age, body mass index, ischemia time, tumor size, amount of hemorrhage, and procedure time. Both groups had a significantly higher DMSA uptake at the preoperative period compared with the postoperative period (postoperative day 1, day 15, month 6, and month 12) (p 0.001). However, both groups had similar DMSA uptake results at the postoperative period. Preoperative and postoperative creatinine levels were not significantly different from each other in both groups. Conclusion: Based on tumor localization, nephron sparing surgery without use of superficial cooling appears as a viable option for small renal masses.展开更多
基金supported by the National Natural Science Foundation of China(No.81070557)
文摘The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury(IRI) in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for 60 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups: sham-operated group(sham), IRI+saline group(IRI group), IRI+Fenofibrate(FEN) group. Normal saline or Fenofibrate(3 mg/kg) was intravenously injected 60 min before renal ischemia in IRI group and FEN group, respectively. Blood samples and renal tissues were collected at the end of reperfusion. The renal function, histopathologic changes, and the expression levels of pro-inflammatory cytokines [interleukin-8(IL-8), tumor necrosis factor alpha(TNF-α) and IL-6] in serum and renal tissue homogenate were assessed. Moreover, the effects of Fenofibrate on activating phosphoinositide 3 kinase/protein kinase B(PI3K/Akt) signaling and peroxisome proliferator-activated receptor-α(PPAR-α) were also measured in renal IRI. The results showed that plasma levels of blood urea nitrogen and creatinine, histopathologic scores and the expression levels of TNF-α, IL-8 and IL-6 were significantly lower in FEN group than in IRI group. Moreover, Fenofibrate pretreatment could further induce PI3K/Akt signal pathway and PPAR-α activation following renal IRI. These findings indicated PPAR-α activation by Fenofibrate exerts protective effects on renal IRI in mice by suppressing inflammation via PI3K/Akt activation. Thus, Fenofibrate could be a novel therapeutic alternative in renal IRI.
基金Supported by A grant from Tehran Medical Sciences University
文摘AIM:To assess the hepatic changes after induction of different periods of renal ischemia. METHODS:Rats were subjected to either sham operation or ischemia (30,45 and 60 min) followed by 60 min reperfusion. Liver and renal functional indices were measured. Hepatic glutathione (GSH) and ferric reducing antioxidant power levels and the concentration of interleukin (IL)-10 and tumor necrosis factor (TNF-α) were evaluated. Portions of liver and kidney tissues were fixed for histological evaluation. RESULTS:Forty-five minutes renal ischemia followed by 60 min reperfusion caused significant changes in liver structure and a significant reduction in renalfunction. These rats showed a significant decrease in liver GSH,as well as a significant increase in TNF-α and IL-10 concentrations. These results demonstrated that renal ischemia caused changes in liver histology,function,oxidative stress and inflammatory status,which led to a reduction in hepatic antioxidant capacity. With 30 min ischemia,the magnitude of these changes was less than those with 45 or 60 min ischemia.CONCLUSION:A minimum of 45 min ischemia is needed to study the effects of renal injury on the liver as a remote organ.
基金supported by grants from Hubei Provincial Natural Science Foundation of China(No.2019CFB805)National Natural Science Foundation of China(No.81670240 and No.81873467).
文摘Objective:To investigate glucose metabolic alterations in cerebral cortical subareas using ^(18)F-labeled glucose derivative fluorodeoxyglucose(FDG)micro-positron emission tomography(PET)scanning in a rat renal ischemia/reperfusion(RIR)model.Methods:Small-animal PET imaging in vivo was performed with ^(18)F-labeled FDG as a PET tracer to identify glucose metabolic alterations in cerebral cortical subregions using a rat model of RIR.Results:We found that the average standardized uptake value(SUV_(average))of the cerebral cortical subareas in the RIR group was significantly increased compared to the sham group(P<0.05).We also found that glucose uptake in different cortical subregions including the left auditory cortex,right medial prefrontal cortex,right para cortex,left retrosplenial cortex,right retrosplenial cortex,and right visual cortex was significantly increased in the RIR group(P<0.05),but there was no significant difference in the SUV_(avcrage) of right auditory cortex,left medial prefrontal cortex,left para cortex,and left visual cortex between the two groups.Conclusion:The ^(18)F-FDG PET data suggests that RIR causes a profound shift in the metabolic machinery of cerebral cortex subregions.
基金This study was supported by the Opening Project of Key Laboratory of Evidence-Identifying in Universities of Shandong,Shandong University of Political Science and Law,China(2018KFKT2 to GX)the Research and Training Projects of Jiaxing University Medical College,China(JUMC2020-06 to DC)+1 种基金the Youth Innovative Research Team Program of Shandong Universities(2019KJE018 to XL)the Key R&D Projects of Shandong Province(2019RKB1034 to XL).
文摘Background:Peroxiredoxin-3(Prx-3)is known to be involved in the clearance of cellular hydrogen peroxide and plays an important role in protecting the myocardial tissue against damage of oxidative stress.However,the role of Prx-3 in protecting the myocardial tissue against renal ischemia/reperfusion(I/R)-induced myocardial injury(RI/RMI)remains unknown.We aimed to examine the antioxidative effect of Prx-3 using a rat RI/RMI model in an attempt to find a new approach to the prevention and treatment of myocardial injury induced by renal I/R.Methods:A RI/RMI rat model was established to detect the renal histopathology and renal functions by hematoxylin-eosin staining staining and commercially available assay kits.The myocardial antioxidant activity and the expressions of mRNA and protein of Prx-3 in the myocardial tissue were measured by real-time polymerase chain reaction and Western blotting assay,respectively.Results:Compared with the normal and control groups,the serum level of blood urea nitrogen and serum creatinine was significantly increased in the I/R group(P<0.05).Histopathological changes in the kidneys were also more obvious,including glomerular cystic and renal interstitial hemorrhage,renal tubular epithelial cell edema,and tubular type formation.The mRNA and protein expressions of Prx-3 were increased significantly in the RI/MRI rat model as compared with those in the normal and control groups.Conclusion:Oxidative damage occurred in the remote myocardium after renal I/R and Prx-3 was able to enhance the self-regulatory ability of the myocardium against damage from oxidative stress after RI/MRI.
文摘Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group,IRI group, empty plasmid group and AM group. One week after re-
基金funded by the Henan Province Education Departent Natural Science Research Item(2010A320020)
文摘Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue.Methods:Fourty eight rats were randomly divided into four groups(n=12):sham operation group,30 min ischemia 60 min reperfusion group,60 min ischemia 60 min reperfusion group,and120 min ischemia 60 min reperfusion group.The brain tissues were taken after the experiment.TUNEL assay was used to detect the brain cell apoptosis,and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemiareperiusion induced apoptosis of brain tissues,and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreased Bcl-2 expression,increased Bax expression,upreguiated expression of NF- κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage,manifested as induced brain tissues apoptosis and inflammation activation.
基金the Scientific Foundation of Ministry of Health of China,No.98-2-283Shanghai Natural Science Foundation,No.98ZB14025
文摘AIM To evaluale the potential role of P-selectinand anti-P-selectin monoclonal antibody(mAb)in apoptosis during hepatic/renal ischemia-reperfusion injury.METHODS Plasma P-selectin level,hepatic/renal P-selectin expression and cell apoptosiswere detected in rat model of hepatic/ renalischemia-reperfusion injury.ELISA,immunohist-ochemistry and TUNEL were used.Someischemia-reperfusion rats were treated with anti-P-selectin mAb.RESULTS Hepatic/renal function insuffic-iency,up-regulated expression of P-selectin inplasma and hepatic/renal tissue,hepatic/renalhistopathological damages and cell apoptosiswere found in rats with hepatic/renal ischemia-reperfusion injury,while these changes becameless conspicuous in animals treated with anti-P-selectin mAb.CONCLUSION P-selectin might mediateneutrophil infiltration and cell apoptosis andcontribute to hepatic/renal ischemia-reperfusioninjury,anti-P-selectin mAb might be an efficientapproach for the prevention and treatment ofhepatic/renal ischemia-reperfusion injury.
文摘Background Ascorbic acid has important antioxidant ischemic preconditioning on later ischemia-reperfusion ascorbic acid in ischemic preconditioning in the kidney. properties, and may play a role in the protective effects of Herein, we examined the role of endogenous extracellular Methods We developed a solitary rabbit kidney model where animals received ischemia-reperfusion only (ischemia-reperfusion group, n=-15) or ischemic preconditioning followed by ischemia-reperfusion (ischemic preconditioning group, n=15). Ischemia-reperfusion was induced by occluding and loosening of the renal pedicle. The process of ischemic preconditioning included 15-minute brief ischemia and 10-minute reperfusion. In vivo microdialysis coupled with online electrochemical detection was used to determine levels of endogenous extracellular ascorbic acid in both groups. The extent of tissue damage was determined in kidney sections stained with hematoxylin and eosin. Serum creatinine and urea nitrogen were also detected to assess renal function. Results During ischemia-reperfusion, the extracellular ascorbic acid concentration during ischemia increased rapidly to the peak level ((130.01±9.98)%), and then decreased slowly to near basal levels. Similar changes were observed during reperfusion (peak level, (126.78±18.24)%). In the ischemic preconditioning group there was a similar pattern of extracellular ascorbic acid concentration during ischemic preconditioning. However, the ascorbic acid level was significantly lower during the ischemia and early reperfusion stage compared to the ischemia-reperfusion group. Additionally, the extent of glomerular ischemic collapse, tubular dilation, tubular denudation, and loss of brush border were markedly attenuated in the ischemic preconditioning group. Levels of serum creatinine and urea nitrogen were also decreased significantly in the ischemic preconditioning group. Conclusions Ischemic preconditioning may protect renal tissue against ischemia-reperfusion injury via use of extracellular ascorbic acid. In vivo microdialysis coupled with online electrochemical detection is effective for continuous monitoring extracellular ascorbic acid in the renal cortex.
文摘Objective: To examine the effect of warm and cold ischemia on functions of the operated kidney in cases with a normal contralateral kidney undergoing nephron sparing surgery. Methods: This study enrolled 40 patients with a normal contralateral kidney and without a renal function threatening risk factor, who were operated with NSS. The patients were randomized at admission. They were divided into 2 equal groups as warm and cold ischemia. An ice application for 10 minutes was done to cold ischemia group after clamping renal artery. Renal functions were evaluated with Technesium-99m-Dimercaptosuccinic Acid (DMSA) and serum creatinine at the preoperative and postoperative (day 1, day 15, month 6, and month 12) period. Statistical analysis was done with Mann Whitney U test, Wilcoxon Signed Rank test, and Fredman test. A p value below 0.05 was considered statistically significant. Results: There were no significant differences between the groups in terms of age, body mass index, ischemia time, tumor size, amount of hemorrhage, and procedure time. Both groups had a significantly higher DMSA uptake at the preoperative period compared with the postoperative period (postoperative day 1, day 15, month 6, and month 12) (p 0.001). However, both groups had similar DMSA uptake results at the postoperative period. Preoperative and postoperative creatinine levels were not significantly different from each other in both groups. Conclusion: Based on tumor localization, nephron sparing surgery without use of superficial cooling appears as a viable option for small renal masses.