Acute Kidney Injury (AKI) is a condition that causes nephrotoxicity in kidney tissues due to cisplatin-induced cancer treatments. Hence, it is proposed in this review that AVE0991 (a MAS-receptor Angiotensin II (1-7) ...Acute Kidney Injury (AKI) is a condition that causes nephrotoxicity in kidney tissues due to cisplatin-induced cancer treatments. Hence, it is proposed in this review that AVE0991 (a MAS-receptor Angiotensin II (1-7) agonist) may reduce cisplatin-induced acute kidney injury by promoting nitric oxide production.展开更多
AIM:To assess the effect of inhibition of caspase-1 on acute renal injury in rats with severe acute pancreatitis(SAP).METHODS:Forty-two Sprague-Dawley rats were randomly divided into three groups:healthy controls(HC,n...AIM:To assess the effect of inhibition of caspase-1 on acute renal injury in rats with severe acute pancreatitis(SAP).METHODS:Forty-two Sprague-Dawley rats were randomly divided into three groups:healthy controls(HC,n=6),SAP rats treated with saline(SAP-S,n=18),or SAP rats treated with a caspase-1/interleukin(IL)-1β-converting-enzyme(ICE)inhibitor(SAP-I-ICE,n=18).SAP was induced by retrograde infusion of 5%sodium taurocholate into the bile-pancreatic duct.HC rats were subjected to identical treatment and surgical procedures without sodium taurocholate.Rats received an intraperitoneal injection of isotonic saline(SAP-S)or the inhibitor(SAP-ICE-I)at 2 and 12 h after induction of acute pancreatitis.Surviving rats were sacrificed at different time points after SAP induction;all samples were obtained and stored for subsequent analyses.The levels of blood urea nitrogen(BUN)and creatinine(Cr)were measured using automatic methods,and serum IL-1βconcentrations were measured by an enzymelinked immunosorbent assay.Intrarenal expression of IL-1β,IL-18 and caspase-1 mRNAs was detected by RT-PCR.IL-1βprotein expression and the pathologic changes in kidney tissues were observed by microscopy after immunohistochemical or hematoxylin and eosin staining,respectively.RESULTS:The serum levels of BUN and Cr in the SAP-S group were 12.48±2.30 mmol/L and 82.83±13.89μmol/L at 6 h,23.53±2.58 mmol/L and 123.67±17.67μmol/L at 12 h,and 23.60±3.33 mmol/L and125.33±21.09μmol/L at 18 h,respectively.All were significantly increased compared to HC rats(P<0.01for all).Levels in SAP-ICE-I rats were significantly decreased compared to SAP-S rats both at 12 and 18 h(P<0.01 for all).Serum IL-1βlevels in the SAP-S group were 276.77±44.92 pg/mL at 6 h,308.99±34.95pg/mL at 12 h,and 311.60±46.51 pg/mL at 18 h;all significantly higher than those in the HC and SAP-ICE-I groups(P<0.01 for all).Intrarenal expression of IL-1βmRNA was weak in HC rats,but increased significantly in SAP-S rats(P<0.01).ICE inhibition significantly decreased the expression of IL-1βand IL-18 mRNAs(P<0.05 for all vs SAP-S),whereas caspase-1 mRNA expression was not significantly different.Weak IL-1βimmunostaining was observed in HC animals,and marked staining was found in the SAP-S group mainly in renal tubular epithelial cells.IL-1βimmunostaining was significantly descended in SAP-ICE-I rats compared to SAP-S rats(P<0.05).Caspase-1 inhibition had no effect on the severity of kidney tissue destruction.CONCLUSION:The expression of caspase-1-activated cytokines IL-1βand IL-18 plays a pivotal role in acute renal injury in rats with experimental SAP.Caspase-1inhibition improves renal function effectively.展开更多
The expression of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of heroin-induced acute lung injury (ALI) in rats was investigated. The model of ALI was established by intravenous injection of heroin ...The expression of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of heroin-induced acute lung injury (ALI) in rats was investigated. The model of ALI was established by intravenous injection of heroin into tail vein in rats. Thirty-six rats were randomly divided into heroin-treated groups (1 h, 2 h, 4 h, 6 h and 24 h) and normal control group. Changes in histopathologic morphology and biological markers of ALI were measured. The expression of ICAM-1 in lung tissue was detected by using immunohistochemistry and RT-PCR. The results showed that the W/D ratio and protein contents in BALF of the heroin-treated groups were significantly higher than that of the control group (P<0.01). The histopathological changes in the lung tissue were more obvious in heroin-treated groups. The ICAM-1 protein and mRNA expression in the lung tissue of heroin-treated groups were significantly increased as compared with that of the control group (P<0.01), and correlated with the ALI parameters in a time-dependent manner. Increasing of ICAM-1 expression was involved in the formation of heroin-induced lung injury. Furthermore, the level of expression was positively correlated with the severity of lung injury.展开更多
BACKGROUND:Platelet endothelial cell adhesion molecule-1(PECAM-1),also known as CD31,is mainly distributed in vascular endothelial cells.Studies have shown that PECAM-1 is a very significant indicator of angiogenesis,...BACKGROUND:Platelet endothelial cell adhesion molecule-1(PECAM-1),also known as CD31,is mainly distributed in vascular endothelial cells.Studies have shown that PECAM-1 is a very significant indicator of angiogenesis,and has been used as an indicator for vascular endothelial cells.The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury(ALI) and fibrosis in paraquat(PQ) induced lung injury in rabbits.METHODS:Thirty-six adult New Zealand rabbits were randomly divided into three groups(12rabbits in each group) according to PQ dosage:8 mg/kg(group A),16 mg/kg(group B),and 32 mg/kg(group C).After PQ infusion,the rabbits were monitored for 7 days and then euthanized.The lungs were removed for histological evaluation.Masson staining was used to determine the degree of lung fibrosis(LF),and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1.Pearson's product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF.RESULTS:Rabbits in the three groups showed apparent poisoning.The rabbits survived longer in group A than in groups B and C(6.47±0.99 days vs.6.09±1.04 days vs.4.77±2.04 days)(P<0.05).ALI score was lower in group A than in groups B and C(8.33±1.03 vs.9.83±1.17 vs.11.50±1.38)(P<0.05),and there was statistically significant difference between group B and group C(P=0.03).LF was slighter in group A than in groups B and C(31.09%±2.05%vs.34.37%±1.62%vs.36.54%±0.44%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.026).The PEACAM-1 expression was higher in group A than in groups B and C(20.31%±0.70%vs.19.34%±0.68%vs.18.37%±0.46%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.017).Pearson's correlation analysis showed that the expression of PECAM-1 was negatively correlated to both ALI score(Coe=-0.732,P=0.001)and degree of LF(Coe=-0.779,P<0.001).CONCLUSIONS:The PECAM-1 expression significantly decreases in New Zealand rabbits after PQ poisoning,and the decrease is dose-dependent.The PECAM-1 expression is negatively correlated with ALI score and LF,showing a significant role in the development of lung injuries induced by PQ.展开更多
CD38 is known to play roles in various inflammatory pathways.However,whether it has a protective or detrimental effect during bacterial septicemia remains disputed.Herein,this study aimed to determine the potential ef...CD38 is known to play roles in various inflammatory pathways.However,whether it has a protective or detrimental effect during bacterial septicemia remains disputed.Herein,this study aimed to determine the potential effect of CD38 on renal injury in septicemia.Escherichia coli(E.coli)was used to induce sepsis-associated renal injury in mice.WT and CD38-/-mice were stimulated with E.coli.After three hours,the serum was collected to detect renal function.Function mRNA expressions inflammatory cytokines in kidneys were quantified by real-time PCR.Hematoxylin and eosin staining were used to observe the histomorphology of kidney.The expression of TLR4,NF-κB,MAPK and cytokines were detected by Western Blot.Our results demonstrated that 3×10^(8) cfu/mL E.coli is the appropriate dose to induce sepsis mice model.Compared to WT sepsis mice,CD38-/-mice showed aggravated kidney injuries with impaired renal function,increased inflammation and apoptosis after E.coli stimulation.Interestingly,CD38 deficiency also led to elevated expression of TLR4 and increased phosphorylation of NF-κB p65/p105 and ERK1/2.To sum up,our results suggested that CD38 deficiency could aggravate E.coli-induced renal injury through activating ERK1/2-NF-κB signaling pathway.展开更多
文摘Acute Kidney Injury (AKI) is a condition that causes nephrotoxicity in kidney tissues due to cisplatin-induced cancer treatments. Hence, it is proposed in this review that AVE0991 (a MAS-receptor Angiotensin II (1-7) agonist) may reduce cisplatin-induced acute kidney injury by promoting nitric oxide production.
文摘AIM:To assess the effect of inhibition of caspase-1 on acute renal injury in rats with severe acute pancreatitis(SAP).METHODS:Forty-two Sprague-Dawley rats were randomly divided into three groups:healthy controls(HC,n=6),SAP rats treated with saline(SAP-S,n=18),or SAP rats treated with a caspase-1/interleukin(IL)-1β-converting-enzyme(ICE)inhibitor(SAP-I-ICE,n=18).SAP was induced by retrograde infusion of 5%sodium taurocholate into the bile-pancreatic duct.HC rats were subjected to identical treatment and surgical procedures without sodium taurocholate.Rats received an intraperitoneal injection of isotonic saline(SAP-S)or the inhibitor(SAP-ICE-I)at 2 and 12 h after induction of acute pancreatitis.Surviving rats were sacrificed at different time points after SAP induction;all samples were obtained and stored for subsequent analyses.The levels of blood urea nitrogen(BUN)and creatinine(Cr)were measured using automatic methods,and serum IL-1βconcentrations were measured by an enzymelinked immunosorbent assay.Intrarenal expression of IL-1β,IL-18 and caspase-1 mRNAs was detected by RT-PCR.IL-1βprotein expression and the pathologic changes in kidney tissues were observed by microscopy after immunohistochemical or hematoxylin and eosin staining,respectively.RESULTS:The serum levels of BUN and Cr in the SAP-S group were 12.48±2.30 mmol/L and 82.83±13.89μmol/L at 6 h,23.53±2.58 mmol/L and 123.67±17.67μmol/L at 12 h,and 23.60±3.33 mmol/L and125.33±21.09μmol/L at 18 h,respectively.All were significantly increased compared to HC rats(P<0.01for all).Levels in SAP-ICE-I rats were significantly decreased compared to SAP-S rats both at 12 and 18 h(P<0.01 for all).Serum IL-1βlevels in the SAP-S group were 276.77±44.92 pg/mL at 6 h,308.99±34.95pg/mL at 12 h,and 311.60±46.51 pg/mL at 18 h;all significantly higher than those in the HC and SAP-ICE-I groups(P<0.01 for all).Intrarenal expression of IL-1βmRNA was weak in HC rats,but increased significantly in SAP-S rats(P<0.01).ICE inhibition significantly decreased the expression of IL-1βand IL-18 mRNAs(P<0.05 for all vs SAP-S),whereas caspase-1 mRNA expression was not significantly different.Weak IL-1βimmunostaining was observed in HC animals,and marked staining was found in the SAP-S group mainly in renal tubular epithelial cells.IL-1βimmunostaining was significantly descended in SAP-ICE-I rats compared to SAP-S rats(P<0.05).Caspase-1 inhibition had no effect on the severity of kidney tissue destruction.CONCLUSION:The expression of caspase-1-activated cytokines IL-1βand IL-18 plays a pivotal role in acute renal injury in rats with experimental SAP.Caspase-1inhibition improves renal function effectively.
文摘The expression of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of heroin-induced acute lung injury (ALI) in rats was investigated. The model of ALI was established by intravenous injection of heroin into tail vein in rats. Thirty-six rats were randomly divided into heroin-treated groups (1 h, 2 h, 4 h, 6 h and 24 h) and normal control group. Changes in histopathologic morphology and biological markers of ALI were measured. The expression of ICAM-1 in lung tissue was detected by using immunohistochemistry and RT-PCR. The results showed that the W/D ratio and protein contents in BALF of the heroin-treated groups were significantly higher than that of the control group (P<0.01). The histopathological changes in the lung tissue were more obvious in heroin-treated groups. The ICAM-1 protein and mRNA expression in the lung tissue of heroin-treated groups were significantly increased as compared with that of the control group (P<0.01), and correlated with the ALI parameters in a time-dependent manner. Increasing of ICAM-1 expression was involved in the formation of heroin-induced lung injury. Furthermore, the level of expression was positively correlated with the severity of lung injury.
基金supported by grants from Guangdong Medical Research Fund(2010501)Guangzhou Pharmaceutical Health Science Fund(2009-YB-111)
文摘BACKGROUND:Platelet endothelial cell adhesion molecule-1(PECAM-1),also known as CD31,is mainly distributed in vascular endothelial cells.Studies have shown that PECAM-1 is a very significant indicator of angiogenesis,and has been used as an indicator for vascular endothelial cells.The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury(ALI) and fibrosis in paraquat(PQ) induced lung injury in rabbits.METHODS:Thirty-six adult New Zealand rabbits were randomly divided into three groups(12rabbits in each group) according to PQ dosage:8 mg/kg(group A),16 mg/kg(group B),and 32 mg/kg(group C).After PQ infusion,the rabbits were monitored for 7 days and then euthanized.The lungs were removed for histological evaluation.Masson staining was used to determine the degree of lung fibrosis(LF),and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1.Pearson's product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF.RESULTS:Rabbits in the three groups showed apparent poisoning.The rabbits survived longer in group A than in groups B and C(6.47±0.99 days vs.6.09±1.04 days vs.4.77±2.04 days)(P<0.05).ALI score was lower in group A than in groups B and C(8.33±1.03 vs.9.83±1.17 vs.11.50±1.38)(P<0.05),and there was statistically significant difference between group B and group C(P=0.03).LF was slighter in group A than in groups B and C(31.09%±2.05%vs.34.37%±1.62%vs.36.54%±0.44%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.026).The PEACAM-1 expression was higher in group A than in groups B and C(20.31%±0.70%vs.19.34%±0.68%vs.18.37%±0.46%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.017).Pearson's correlation analysis showed that the expression of PECAM-1 was negatively correlated to both ALI score(Coe=-0.732,P=0.001)and degree of LF(Coe=-0.779,P<0.001).CONCLUSIONS:The PECAM-1 expression significantly decreases in New Zealand rabbits after PQ poisoning,and the decrease is dose-dependent.The PECAM-1 expression is negatively correlated with ALI score and LF,showing a significant role in the development of lung injuries induced by PQ.
基金supported by the National Natural Sciences Foundation of China (NSFC) grant numbers [31960165&81760288]
文摘CD38 is known to play roles in various inflammatory pathways.However,whether it has a protective or detrimental effect during bacterial septicemia remains disputed.Herein,this study aimed to determine the potential effect of CD38 on renal injury in septicemia.Escherichia coli(E.coli)was used to induce sepsis-associated renal injury in mice.WT and CD38-/-mice were stimulated with E.coli.After three hours,the serum was collected to detect renal function.Function mRNA expressions inflammatory cytokines in kidneys were quantified by real-time PCR.Hematoxylin and eosin staining were used to observe the histomorphology of kidney.The expression of TLR4,NF-κB,MAPK and cytokines were detected by Western Blot.Our results demonstrated that 3×10^(8) cfu/mL E.coli is the appropriate dose to induce sepsis mice model.Compared to WT sepsis mice,CD38-/-mice showed aggravated kidney injuries with impaired renal function,increased inflammation and apoptosis after E.coli stimulation.Interestingly,CD38 deficiency also led to elevated expression of TLR4 and increased phosphorylation of NF-κB p65/p105 and ERK1/2.To sum up,our results suggested that CD38 deficiency could aggravate E.coli-induced renal injury through activating ERK1/2-NF-κB signaling pathway.
