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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

SIRT protein expression and activity in the small intestine tissue of healthy rats. After 7 days' administration of PD or Ex527 (a selective SIRT1 inhibitor), levels of both the SIRT1 protein (a) and activity (b) were markedly increased in the PD group but were all reduced in the Ex527 group (n = 8 per group). aaP < 0.01 compared with the sham group; bbP < 0.01 compared with the PD group. SIRT1, silent information regulator 1; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; PD, polydatin.
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fig6: SIRT protein expression and activity in the small intestine tissue of healthy rats. After 7 days' administration of PD or Ex527 (a selective SIRT1 inhibitor), levels of both the SIRT1 protein (a) and activity (b) were markedly increased in the PD group but were all reduced in the Ex527 group (n = 8 per group). aaP < 0.01 compared with the sham group; bbP < 0.01 compared with the PD group. SIRT1, silent information regulator 1; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; PD, polydatin.

Mentions: We first evaluated the effects of PD and Ex527 on intestine in sham-operated rats. We found that after intraperitoneal administration of the two agents at experimental dosage for 7 days, SIRT1 protein level and activity were markedly increased in the PD administration group but significantly decreased in the Ex527 group (P < 0.01 for both groups versus sham, Figure 6).


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)

SIRT protein expression and activity in the small intestine tissue of healthy rats. After 7 days' administration of PD or Ex527 (a selective SIRT1 inhibitor), levels of both the SIRT1 protein (a) and activity (b) were markedly increased in the PD group but were all reduced in the Ex527 group (n = 8 per group). aaP < 0.01 compared with the sham group; bbP < 0.01 compared with the PD group. SIRT1, silent information regulator 1; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; PD, polydatin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: SIRT protein expression and activity in the small intestine tissue of healthy rats. After 7 days' administration of PD or Ex527 (a selective SIRT1 inhibitor), levels of both the SIRT1 protein (a) and activity (b) were markedly increased in the PD group but were all reduced in the Ex527 group (n = 8 per group). aaP < 0.01 compared with the sham group; bbP < 0.01 compared with the PD group. SIRT1, silent information regulator 1; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; PD, polydatin.
Mentions: We first evaluated the effects of PD and Ex527 on intestine in sham-operated rats. We found that after intraperitoneal administration of the two agents at experimental dosage for 7 days, SIRT1 protein level and activity were markedly increased in the PD administration group but significantly decreased in the Ex527 group (P < 0.01 for both groups versus sham, Figure 6).

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