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Ulinastatin preconditioning attenuates inflammatory reaction of hepatic ischemia reperfusion injury in rats via high mobility group box 1(HMGB1) inhibition.

Tong Y, Tang Z, Yang T, Yang Y, Yang L, Shen W, Chen W - Int J Med Sci (2014)

Bottom Line: Objective It has been found that ulinastatin (UTI) can attenuate hepatic injury in a rat model of ischemia reperfusion (IR), but the specific mechanism is unclear.Results Serum levels of aminotransferases, cytokines and hepatic MPO in UPC and UPC+anti-HMGB1 groups were significantly lower than those in control group (p<0.05).Conclusions HMGB1 expressions in UPC and UPC+anti-HMGB1 groups were significantly lower than those in the two control groups (p<0.05), pretreatment with ulinastatin attenuated liver IR injury by reducing HMGB1 expression through its anti-inflammatory effects.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Liver Surgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, 1630 Dongfang Road, Shanghai 200127, China.

ABSTRACT
Objective It has been found that ulinastatin (UTI) can attenuate hepatic injury in a rat model of ischemia reperfusion (IR), but the specific mechanism is unclear. This study aims to investigate possible pathomechanism of ulinastatin in reducing the inflammatory response after hepatic IR. Methods A male sprague-dawley(SD) rat model of hepatic ischemia reperfusion injury was used. The rats were randomly divided into 4 groups on average, which were 0.9% saline and IR group as control, ulinastatin preconditioning (UPC) group, UPC+rHMGB1 (recombinant HMGB1) group and UPC +anti-HMGB1 group. Serum aminotransferases, TNF-α, IL-1 and Myeloperoxidase (MPO) levels were measured. Histopathology examination and apoptotic cell detection and the different expression of HMGB1 protein were also assessed. Results Serum levels of aminotransferases, cytokines and hepatic MPO in UPC and UPC+anti-HMGB1 groups were significantly lower than those in control group (p<0.05). Decreased histologic damage and apoptosis were also seen in these two groups (p<0.05). Conclusions HMGB1 expressions in UPC and UPC+anti-HMGB1 groups were significantly lower than those in the two control groups (p<0.05), pretreatment with ulinastatin attenuated liver IR injury by reducing HMGB1 expression through its anti-inflammatory effects.

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Serum aminotransferases, cytokines, and hepatic myeloperoxidase among different groups. Figure A showed serum ALT and AST levels significantly increased when 20 IU/ml of l.5ml/kg of ulinastatin pretreated ( UPC ) group or combined with 100μg of anti-HMGB1 (UPC+Anti-HMGB1 group) compared to those in control (p<0.05), but there was no significant difference between control group and UPC+rHMGB1 group (p>0.05). As showed in figure B and C, significantly increasing serum cytokines TNF-α and IL-1 levels were found in the control group and the UPC+rHMGB1 group compared with UPC group and UPC+Anti-HMGB1 group (p<0.05). At 120 min after reperfusion, rats in UPC and UPC plus Anti-HMGB1 had significantly reduced levels of myeloperoxidase (MDA) in liver homogenates compared to those in control as showed in figure D. Values are mean ± SD of 10 animals in each group. * P < 0.05 vs. Control.
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Figure 1: Serum aminotransferases, cytokines, and hepatic myeloperoxidase among different groups. Figure A showed serum ALT and AST levels significantly increased when 20 IU/ml of l.5ml/kg of ulinastatin pretreated ( UPC ) group or combined with 100μg of anti-HMGB1 (UPC+Anti-HMGB1 group) compared to those in control (p<0.05), but there was no significant difference between control group and UPC+rHMGB1 group (p>0.05). As showed in figure B and C, significantly increasing serum cytokines TNF-α and IL-1 levels were found in the control group and the UPC+rHMGB1 group compared with UPC group and UPC+Anti-HMGB1 group (p<0.05). At 120 min after reperfusion, rats in UPC and UPC plus Anti-HMGB1 had significantly reduced levels of myeloperoxidase (MDA) in liver homogenates compared to those in control as showed in figure D. Values are mean ± SD of 10 animals in each group. * P < 0.05 vs. Control.

Mentions: As shown in Figure 1, serum ALT and AST levels significantly decreased in UPC group and UPC+Anti-HMGB1 group compared with control group (p<0.05). However, there was no significant difference between control and UPC+rHMGB1 group (p>0.05). Serum ALT and AST levels in UPC group were comparable to those in UPC+Anti-HMGB1 group (p>0.05). Significantly increasing serum cytokines TNF-α and IL-1 levels were found in the control group and the UPC+rHMGB1 group compared with UPC group and UPC+Anti-HMGB1 group (p<0.05), but the differences between control group and the UPC+rHMGB1 group were not statistically significant (p>0.05). The UPC+Anti-HMGB1 group had similar serum cytokines TNF-α and IL-1 levels compared with UPC group (p>0.05). At 120 mins after reperfusion, rats pretreated with UPC and UPC plus Anti-HMGB1 had significantly reduced levels of MDA in liver homogenates compared to those in control.


Ulinastatin preconditioning attenuates inflammatory reaction of hepatic ischemia reperfusion injury in rats via high mobility group box 1(HMGB1) inhibition.

Tong Y, Tang Z, Yang T, Yang Y, Yang L, Shen W, Chen W - Int J Med Sci (2014)

Serum aminotransferases, cytokines, and hepatic myeloperoxidase among different groups. Figure A showed serum ALT and AST levels significantly increased when 20 IU/ml of l.5ml/kg of ulinastatin pretreated ( UPC ) group or combined with 100μg of anti-HMGB1 (UPC+Anti-HMGB1 group) compared to those in control (p<0.05), but there was no significant difference between control group and UPC+rHMGB1 group (p>0.05). As showed in figure B and C, significantly increasing serum cytokines TNF-α and IL-1 levels were found in the control group and the UPC+rHMGB1 group compared with UPC group and UPC+Anti-HMGB1 group (p<0.05). At 120 min after reperfusion, rats in UPC and UPC plus Anti-HMGB1 had significantly reduced levels of myeloperoxidase (MDA) in liver homogenates compared to those in control as showed in figure D. Values are mean ± SD of 10 animals in each group. * P < 0.05 vs. Control.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3936027&req=5

Figure 1: Serum aminotransferases, cytokines, and hepatic myeloperoxidase among different groups. Figure A showed serum ALT and AST levels significantly increased when 20 IU/ml of l.5ml/kg of ulinastatin pretreated ( UPC ) group or combined with 100μg of anti-HMGB1 (UPC+Anti-HMGB1 group) compared to those in control (p<0.05), but there was no significant difference between control group and UPC+rHMGB1 group (p>0.05). As showed in figure B and C, significantly increasing serum cytokines TNF-α and IL-1 levels were found in the control group and the UPC+rHMGB1 group compared with UPC group and UPC+Anti-HMGB1 group (p<0.05). At 120 min after reperfusion, rats in UPC and UPC plus Anti-HMGB1 had significantly reduced levels of myeloperoxidase (MDA) in liver homogenates compared to those in control as showed in figure D. Values are mean ± SD of 10 animals in each group. * P < 0.05 vs. Control.
Mentions: As shown in Figure 1, serum ALT and AST levels significantly decreased in UPC group and UPC+Anti-HMGB1 group compared with control group (p<0.05). However, there was no significant difference between control and UPC+rHMGB1 group (p>0.05). Serum ALT and AST levels in UPC group were comparable to those in UPC+Anti-HMGB1 group (p>0.05). Significantly increasing serum cytokines TNF-α and IL-1 levels were found in the control group and the UPC+rHMGB1 group compared with UPC group and UPC+Anti-HMGB1 group (p<0.05), but the differences between control group and the UPC+rHMGB1 group were not statistically significant (p>0.05). The UPC+Anti-HMGB1 group had similar serum cytokines TNF-α and IL-1 levels compared with UPC group (p>0.05). At 120 mins after reperfusion, rats pretreated with UPC and UPC plus Anti-HMGB1 had significantly reduced levels of MDA in liver homogenates compared to those in control.

Bottom Line: Objective It has been found that ulinastatin (UTI) can attenuate hepatic injury in a rat model of ischemia reperfusion (IR), but the specific mechanism is unclear.Results Serum levels of aminotransferases, cytokines and hepatic MPO in UPC and UPC+anti-HMGB1 groups were significantly lower than those in control group (p<0.05).Conclusions HMGB1 expressions in UPC and UPC+anti-HMGB1 groups were significantly lower than those in the two control groups (p<0.05), pretreatment with ulinastatin attenuated liver IR injury by reducing HMGB1 expression through its anti-inflammatory effects.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Liver Surgery, Renji Hospital, Shanghai Jiaotong University, School of Medicine, 1630 Dongfang Road, Shanghai 200127, China.

ABSTRACT
Objective It has been found that ulinastatin (UTI) can attenuate hepatic injury in a rat model of ischemia reperfusion (IR), but the specific mechanism is unclear. This study aims to investigate possible pathomechanism of ulinastatin in reducing the inflammatory response after hepatic IR. Methods A male sprague-dawley(SD) rat model of hepatic ischemia reperfusion injury was used. The rats were randomly divided into 4 groups on average, which were 0.9% saline and IR group as control, ulinastatin preconditioning (UPC) group, UPC+rHMGB1 (recombinant HMGB1) group and UPC +anti-HMGB1 group. Serum aminotransferases, TNF-α, IL-1 and Myeloperoxidase (MPO) levels were measured. Histopathology examination and apoptotic cell detection and the different expression of HMGB1 protein were also assessed. Results Serum levels of aminotransferases, cytokines and hepatic MPO in UPC and UPC+anti-HMGB1 groups were significantly lower than those in control group (p<0.05). Decreased histologic damage and apoptosis were also seen in these two groups (p<0.05). Conclusions HMGB1 expressions in UPC and UPC+anti-HMGB1 groups were significantly lower than those in the two control groups (p<0.05), pretreatment with ulinastatin attenuated liver IR injury by reducing HMGB1 expression through its anti-inflammatory effects.

Show MeSH
Related in: MedlinePlus