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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

Serum inflammatory cytokine measurement following severe hemorrhagic shock (n = 8 rats). 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. TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1 beta; IL-6, interleukin-6; PD, polydatin.
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fig7: Serum inflammatory cytokine measurement following severe hemorrhagic shock (n = 8 rats). 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. TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1 beta; IL-6, interleukin-6; PD, polydatin.

Mentions: Finally, we evaluated the effect of PD on general animal condition including the systemic inflammatory response, MAP, and survival time. We found that 2 h after shed blood infusion, serum proinflammatory cytokine levels were elevated (Figure 7), and MAP was sharply decreased (Figure 8(b)). Consequently, all the rats in the vehicle group died within 48 h (Figure 8(a) and Table 1). Notably, PD administration significantly mitigated the inflammatory response, elevated MAP 2 h after shed blood reinfusion, and prolonged the survival time of shock rats. Five of eight rats survived for over 24 h, with a median survival time of 27 h (P < 0.01 versus vehicle group, Figure 8(a) and Table 1). As expected, Ex527 treatment blocked the beneficial effects of PD on system inflammatory mitigation, MAP, and survival time (P < 0.01, Figure 8(a) and Table 1).


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)

Serum inflammatory cytokine measurement following severe hemorrhagic shock (n = 8 rats). 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. TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1 beta; IL-6, interleukin-6; PD, polydatin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig7: Serum inflammatory cytokine measurement following severe hemorrhagic shock (n = 8 rats). 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. TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1 beta; IL-6, interleukin-6; PD, polydatin.
Mentions: Finally, we evaluated the effect of PD on general animal condition including the systemic inflammatory response, MAP, and survival time. We found that 2 h after shed blood infusion, serum proinflammatory cytokine levels were elevated (Figure 7), and MAP was sharply decreased (Figure 8(b)). Consequently, all the rats in the vehicle group died within 48 h (Figure 8(a) and Table 1). Notably, PD administration significantly mitigated the inflammatory response, elevated MAP 2 h after shed blood reinfusion, and prolonged the survival time of shock rats. Five of eight rats survived for over 24 h, with a median survival time of 27 h (P < 0.01 versus vehicle group, Figure 8(a) and Table 1). As expected, Ex527 treatment blocked the beneficial effects of PD on system inflammatory mitigation, MAP, and survival time (P < 0.01, Figure 8(a) and Table 1).

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