Effect of Simvastatin on the Intestinal Rho/ROCK Signaling Pathway in Rats With Sepsis.

Abstract

BACKGROUND:

Simvastatin may alleviate the intestinal barrier dysfunction induced by sepsis. This study aimed to investigate the role of the Ras homolog (Rho)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway in the intestinal barrier of simvastatin-treated rats with sepsis.

MATERIALS AND METHODS:

Male Wistar rats were pretreated with simvastatin (0.2 μg/g of body weight) for 1 week before cecal ligation and puncture. Twenty-four hours after cecal ligation and puncture, the condition of bacterial translocation was evaluated. Plasma levels of intestinal fatty acid binding protein, D-lactic acid and inflammatory factors, and oxidative stress in the intestine were determined. The intestinal injury scores, as well as the protein levels of Rho, ROCK1, and tight junction proteins ZO-1 and occludin were analyzed.

RESULTS:

Treatment with simvastatin alleviated the sepsis-induced increases in the plasma concentration of intestinal fatty acid binding protein and D-lactic acid, as well as the number of colony-forming units in the bacterial culture of the blood, liver, spleen, and kidney. In addition, simvastatin effectively reduced the intestinal levels of tumor necrosis factor α, interleukin-6, high-mobility group box 1, and malondialdehyde and increased the activity of superoxide dismutase in rats with sepsis. Staining with hematoxylin and eosin showed that severe intestinal injury occurred in the sepsis group, which was reduced by the treatment of simvastatin. Furthermore, the expression of Rho and ROCK1 was significantly downregulated and the protein expression levels of ZO-1 and occludin were significantly increased in simvastatin-treated rats (P < 0.05).

CONCLUSIONS:

Simvastatin can ameliorate the intestinal barrier dysfunction caused by sepsis by inhibiting the Rho/ROCK signaling pathway and reducing the levels of inflammatory factors and oxidative stress in the intestine, which also increase the expression of tight junction proteins.

• Authors: Yu Wang, Xiaofeng Wang, Wenping Yang, Xin Zhao, Rong Zhang
• Journal: The Journal of surgical research (J Surg Res) Vol. 232 Pg. 531-538 (12 2018) ISSN: 1095-8673 [Electronic] United States
• PMID: 30463769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Fatty Acid-Binding Proteins
• Tjp1 protein, rat
• Zonula Occludens-1 Protein
• Simvastatin
• ROCK1 protein, rat
• rho-Associated Kinases

Topics

• Animals
• Fatty Acid-Binding Proteins (blood)
• Intestines (drug effects, physiology)
• Male
• Oxidative Stress (drug effects)
• Rats
• Rats, Wistar
• Sepsis (drug therapy)
• Signal Transduction (drug effects)
• Simvastatin (pharmacology)
• Zonula Occludens-1 Protein (analysis)
• rho-Associated Kinases (antagonists & inhibitors, physiology)