Limits...
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

TUNEL apoptosis staining and Bcl-2 and Bax protein levels in the small intestine epithelial following severe shock. (a) TUNEL staining (original magnification ×400). (b) Statistical analysis of TUNEL results (n = 8–10). (c) Representative western blotting for apoptosis-related protein (Bcl-2 and Bax). (d-e) Densitometry analysis of Bcl-2 and Bax (n = 4 per group). aP < 0.05, aaP < 0.01 compared with the control group; bP < 0.05, bbP < 0.01 compared with the vehicle group; cP < 0.05, ccP < 0.01 compared with the PD group. DAPI, 4′,6-diamidino-2-phenylindole; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; HPF, high power field; Bcl-2, B-cell lymphoma-2; Bax, Bcl-2-associated X protein; PD, polydatin.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4537745&req=5

fig2: TUNEL apoptosis staining and Bcl-2 and Bax protein levels in the small intestine epithelial following severe shock. (a) TUNEL staining (original magnification ×400). (b) Statistical analysis of TUNEL results (n = 8–10). (c) Representative western blotting for apoptosis-related protein (Bcl-2 and Bax). (d-e) Densitometry analysis of Bcl-2 and Bax (n = 4 per group). aP < 0.05, aaP < 0.01 compared with the control group; bP < 0.05, bbP < 0.01 compared with the vehicle group; cP < 0.05, ccP < 0.01 compared with the PD group. DAPI, 4′,6-diamidino-2-phenylindole; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; HPF, high power field; Bcl-2, B-cell lymphoma-2; Bax, Bcl-2-associated X protein; PD, polydatin.

Mentions: Next, we determined cell apoptosis in the small intestine. The number of TUNEL+ cells in the vehicle group increased over 10-fold compared to the normal (control) group (P < 0.01, Figures 2(a) and 2(b)). Expression of the proapoptosis protein Bax was increased, and the antiapoptosis protein Bcl-2 was reduced (P < 0.01 for all, Figures 2(c)–2(e)).


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)

TUNEL apoptosis staining and Bcl-2 and Bax protein levels in the small intestine epithelial following severe shock. (a) TUNEL staining (original magnification ×400). (b) Statistical analysis of TUNEL results (n = 8–10). (c) Representative western blotting for apoptosis-related protein (Bcl-2 and Bax). (d-e) Densitometry analysis of Bcl-2 and Bax (n = 4 per group). aP < 0.05, aaP < 0.01 compared with the control group; bP < 0.05, bbP < 0.01 compared with the vehicle group; cP < 0.05, ccP < 0.01 compared with the PD group. DAPI, 4′,6-diamidino-2-phenylindole; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; HPF, high power field; Bcl-2, B-cell lymphoma-2; Bax, Bcl-2-associated X protein; PD, polydatin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: TUNEL apoptosis staining and Bcl-2 and Bax protein levels in the small intestine epithelial following severe shock. (a) TUNEL staining (original magnification ×400). (b) Statistical analysis of TUNEL results (n = 8–10). (c) Representative western blotting for apoptosis-related protein (Bcl-2 and Bax). (d-e) Densitometry analysis of Bcl-2 and Bax (n = 4 per group). aP < 0.05, aaP < 0.01 compared with the control group; bP < 0.05, bbP < 0.01 compared with the vehicle group; cP < 0.05, ccP < 0.01 compared with the PD group. DAPI, 4′,6-diamidino-2-phenylindole; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; HPF, high power field; Bcl-2, B-cell lymphoma-2; Bax, Bcl-2-associated X protein; PD, polydatin.
Mentions: Next, we determined cell apoptosis in the small intestine. The number of TUNEL+ cells in the vehicle group increased over 10-fold compared to the normal (control) group (P < 0.01, Figures 2(a) and 2(b)). Expression of the proapoptosis protein Bax was increased, and the antiapoptosis protein Bcl-2 was reduced (P < 0.01 for all, Figures 2(c)–2(e)).

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