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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

Protein expression of PGC-1α and protein expression and activity of SIRT1 in small intestine tissue following severe shock. (a) PGC-1α and (b) SIRT1 proteins expression in small intestine tissue (n = 4 per group). (c) Relative SIRT1 activity of small intestine tissue (n = 6 per group). aP < 0.05, aaP < 0.01 compared with the control group; bbP < 0.01 compared with the vehicle group; cP < 0.05, ccP < 0.01 compared with the PD group. PGC-1α, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; PD, polydatin.
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fig5: Protein expression of PGC-1α and protein expression and activity of SIRT1 in small intestine tissue following severe shock. (a) PGC-1α and (b) SIRT1 proteins expression in small intestine tissue (n = 4 per group). (c) Relative SIRT1 activity of small intestine tissue (n = 6 per group). aP < 0.05, aaP < 0.01 compared with the control group; bbP < 0.01 compared with the vehicle group; cP < 0.05, ccP < 0.01 compared with the PD group. PGC-1α, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; PD, polydatin.

Mentions: Given the regulatory effect of PGC-1α and SIRT1 on SOD2 and the interaction between PGC-1α and SIRT1, we hypothesized that SOD2 might be modulated by the “PGC-1 α-SIRT1 axis.” We therefore measured PGC-1α protein expression and SIRT1 protein expression and activity. Compared with the control group, the relative protein expressions of PGC-1α and SIRT1 were decreased by 42.5% ± 5.7% and 23% ± 7.1% in the vehicle group, respectively (P < 0.01 for all, Figures 5(a) and 5(b)). As expected, the relative activity of SIRT1 was decreased to less than half that of the control group (P < 0.01, Figure 5(c)). These results showed that both SIRT protein expression and activity were reduced in the small intestine of rats subjected to severe shock.


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)

Protein expression of PGC-1α and protein expression and activity of SIRT1 in small intestine tissue following severe shock. (a) PGC-1α and (b) SIRT1 proteins expression in small intestine tissue (n = 4 per group). (c) Relative SIRT1 activity of small intestine tissue (n = 6 per group). aP < 0.05, aaP < 0.01 compared with the control group; bbP < 0.01 compared with the vehicle group; cP < 0.05, ccP < 0.01 compared with the PD group. PGC-1α, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; PD, polydatin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Protein expression of PGC-1α and protein expression and activity of SIRT1 in small intestine tissue following severe shock. (a) PGC-1α and (b) SIRT1 proteins expression in small intestine tissue (n = 4 per group). (c) Relative SIRT1 activity of small intestine tissue (n = 6 per group). aP < 0.05, aaP < 0.01 compared with the control group; bbP < 0.01 compared with the vehicle group; cP < 0.05, ccP < 0.01 compared with the PD group. PGC-1α, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; PD, polydatin.
Mentions: Given the regulatory effect of PGC-1α and SIRT1 on SOD2 and the interaction between PGC-1α and SIRT1, we hypothesized that SOD2 might be modulated by the “PGC-1 α-SIRT1 axis.” We therefore measured PGC-1α protein expression and SIRT1 protein expression and activity. Compared with the control group, the relative protein expressions of PGC-1α and SIRT1 were decreased by 42.5% ± 5.7% and 23% ± 7.1% in the vehicle group, respectively (P < 0.01 for all, Figures 5(a) and 5(b)). As expected, the relative activity of SIRT1 was decreased to less than half that of the control group (P < 0.01, Figure 5(c)). These results showed that both SIRT protein expression and activity were reduced in the small intestine of rats subjected to severe shock.

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