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Polydatin Alleviates Small Intestine Injury during Hemorrhagic Shock as a SIRT1 Activator.

Zeng Z, Chen Z, Xu S, Song R, Yang H, Zhao KS - Oxid Med Cell Longev (2015)

Bottom Line: SIRT1 activity and PGC-1α protein expression of the small intestine were decreased, which led to an increase in acetylated SOD2 and decreases in the expression and activity of SOD2, resulting in severe oxidative stress.The decreased SIRT1 activity and expression were partially restored in the PD administration group, which showed reduced intestine injury and longer survival time.Notably, the effect of PD was abolished after the addition of Ex527, a selective inhibitor of SIRT1.

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China ; Guangdong Key Lab of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China.

ABSTRACT

Objective: To evaluate the role of SIRT1 in small intestine damage following severe hemorrhagic shock and to investigate whether polydatin (PD) can activate SIRT1 in shock treatment.

Research design and methods: The severe hemorrhagic shock model was reproduced in Sprague Dawley rats.

Main outcome measures: Two hours after drug administration, half of the rats were assessed for survival time evaluation and the remainder were used for small intestinal tissue sample collection.

Results: Bleeding and swelling appeared in the small intestine with epithelial apoptosis and gut barrier disturbance during hemorrhagic shock. SIRT1 activity and PGC-1α protein expression of the small intestine were decreased, which led to an increase in acetylated SOD2 and decreases in the expression and activity of SOD2, resulting in severe oxidative stress. The decreased SIRT1 activity and expression were partially restored in the PD administration group, which showed reduced intestine injury and longer survival time. Notably, the effect of PD was abolished after the addition of Ex527, a selective inhibitor of SIRT1.

Conclusions: The results collectively suggest a role for the SIRT1-PGC-1α-SOD2 axis in small intestine injury following severe hemorrhagic shock and that PD is an effective SIRT1 activator for the shock treatment.

No MeSH data available.


Related in: MedlinePlus

Gross morphologic alterations and histopathologic changes of the small intestine in severe shock rats. (a) Obvious bleeding and swelling appeared in both the vehicle and PD/Ex527 groups, but these were reduced in the PD group. Histologic lesions of the rat small bowel are shown in the bottom two rows. Shortened, broadened villi and extensive denudation of the villus epithelium were seen in the vehicle and PD/Ex527 groups, with mild broadening of the villi and disruption of villus epithelium in the PD group. (b) Chiu injury score of small intestine (n = 6 rats per group). aP < 0.05, aaP < 0.01 compared with the control group, bbP < 0.01 compared with the vehicle group, and ccP < 0.01 compared with the PD group. HE, hematoxylin-eosin staining; PD, polydatin.
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fig1: Gross morphologic alterations and histopathologic changes of the small intestine in severe shock rats. (a) Obvious bleeding and swelling appeared in both the vehicle and PD/Ex527 groups, but these were reduced in the PD group. Histologic lesions of the rat small bowel are shown in the bottom two rows. Shortened, broadened villi and extensive denudation of the villus epithelium were seen in the vehicle and PD/Ex527 groups, with mild broadening of the villi and disruption of villus epithelium in the PD group. (b) Chiu injury score of small intestine (n = 6 rats per group). aP < 0.05, aaP < 0.01 compared with the control group, bbP < 0.01 compared with the vehicle group, and ccP < 0.01 compared with the PD group. HE, hematoxylin-eosin staining; PD, polydatin.

Mentions: First, we determined if small intestine injury took place during severe shock by evaluating intestine histopathology. Hemorrhagic shock for 2 h followed by reperfusion for another 2 h resulted in obvious bleeding and swelling in the small intestine of the vehicle group (Figure 1(a)). Moreover, marked villous stroma broadening, focal necrosis, and some epithelial cell detachment accompanied by marked edema and congestion were observed on histologic evaluation with H&E staining (Figure 1(a)). The Chiu score was also increased (Figure 1(b)). These results collectively indicated that severe intestine injury occurred in severe shock rats.


Polydatin Alleviates Small Intestine Injury during Hemorrhagic Shock as a SIRT1 Activator.

Zeng Z, Chen Z, Xu S, Song R, Yang H, Zhao KS - Oxid Med Cell Longev (2015)

Gross morphologic alterations and histopathologic changes of the small intestine in severe shock rats. (a) Obvious bleeding and swelling appeared in both the vehicle and PD/Ex527 groups, but these were reduced in the PD group. Histologic lesions of the rat small bowel are shown in the bottom two rows. Shortened, broadened villi and extensive denudation of the villus epithelium were seen in the vehicle and PD/Ex527 groups, with mild broadening of the villi and disruption of villus epithelium in the PD group. (b) Chiu injury score of small intestine (n = 6 rats per group). aP < 0.05, aaP < 0.01 compared with the control group, bbP < 0.01 compared with the vehicle group, and ccP < 0.01 compared with the PD group. HE, hematoxylin-eosin staining; PD, polydatin.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537745&req=5

fig1: Gross morphologic alterations and histopathologic changes of the small intestine in severe shock rats. (a) Obvious bleeding and swelling appeared in both the vehicle and PD/Ex527 groups, but these were reduced in the PD group. Histologic lesions of the rat small bowel are shown in the bottom two rows. Shortened, broadened villi and extensive denudation of the villus epithelium were seen in the vehicle and PD/Ex527 groups, with mild broadening of the villi and disruption of villus epithelium in the PD group. (b) Chiu injury score of small intestine (n = 6 rats per group). aP < 0.05, aaP < 0.01 compared with the control group, bbP < 0.01 compared with the vehicle group, and ccP < 0.01 compared with the PD group. HE, hematoxylin-eosin staining; PD, polydatin.
Mentions: First, we determined if small intestine injury took place during severe shock by evaluating intestine histopathology. Hemorrhagic shock for 2 h followed by reperfusion for another 2 h resulted in obvious bleeding and swelling in the small intestine of the vehicle group (Figure 1(a)). Moreover, marked villous stroma broadening, focal necrosis, and some epithelial cell detachment accompanied by marked edema and congestion were observed on histologic evaluation with H&E staining (Figure 1(a)). The Chiu score was also increased (Figure 1(b)). These results collectively indicated that severe intestine injury occurred in severe shock rats.

Bottom Line: SIRT1 activity and PGC-1α protein expression of the small intestine were decreased, which led to an increase in acetylated SOD2 and decreases in the expression and activity of SOD2, resulting in severe oxidative stress.The decreased SIRT1 activity and expression were partially restored in the PD administration group, which showed reduced intestine injury and longer survival time.Notably, the effect of PD was abolished after the addition of Ex527, a selective inhibitor of SIRT1.

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China ; Guangdong Key Lab of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China.

ABSTRACT

Objective: To evaluate the role of SIRT1 in small intestine damage following severe hemorrhagic shock and to investigate whether polydatin (PD) can activate SIRT1 in shock treatment.

Research design and methods: The severe hemorrhagic shock model was reproduced in Sprague Dawley rats.

Main outcome measures: Two hours after drug administration, half of the rats were assessed for survival time evaluation and the remainder were used for small intestinal tissue sample collection.

Results: Bleeding and swelling appeared in the small intestine with epithelial apoptosis and gut barrier disturbance during hemorrhagic shock. SIRT1 activity and PGC-1α protein expression of the small intestine were decreased, which led to an increase in acetylated SOD2 and decreases in the expression and activity of SOD2, resulting in severe oxidative stress. The decreased SIRT1 activity and expression were partially restored in the PD administration group, which showed reduced intestine injury and longer survival time. Notably, the effect of PD was abolished after the addition of Ex527, a selective inhibitor of SIRT1.

Conclusions: The results collectively suggest a role for the SIRT1-PGC-1α-SOD2 axis in small intestine injury following severe hemorrhagic shock and that PD is an effective SIRT1 activator for the shock treatment.

No MeSH data available.


Related in: MedlinePlus