Dexmedetomidine protects against endothelial injury in septic rats induced by cecal ligation and puncture by decreasing angiopoietin 2 and increasing vascular endothelial cadherin levels

Abstract

The aim of the present study was to investigate the protective effect of dexmedetomidine (Dex) on endothelial injury in a cecal ligation and puncture (CLP)-induced rat model of sepsis. A total of 36 male Sprague-Dawley rats were divided into three groups: Sham, CLP and CLP + Dex. The wet/dry (W/D) ratio of lung weight, hematoxylin and eosin (H&E) staining of lung tissue, plasma levels of angiopoietin (Ang)1 and 2, ratio of Ang2/1 and vascular endothelial (VE)-cadherin protein expression levels in lung tissue were determined. The W/D ratio of lung tissue in the CLP + Dex group was significantly lower than that in the CLP group (P<0.01). The H&E staining results indicated that Dex treatment reduced the levels of CLP-induced alveolar septum widening, infiltrating white blood cells and congestion, when compared with CLP alone. In addition, the expression levels of plasma Ang2 and the Ang2/1 ratio in the CLP + Dex group were significantly lower than those of the CLP rats (P<0.01). Furthermore, the level of VE-cadherin protein in lung tissue of the CLP + Dex group was higher than that of the CLP group (P<0.05). The results indicated that Dex had a protective effect against CLP-induced endothelial injury, through the ability to reduce expression of the endothelial injury factor Ang2 and increase the expression of the endothelial adhesion junction factor VE-cadherin in a septic rat model. These data suggest a potential application of Dex in the clinical treatment of sepsis.

Keywords: angiopoietin-1; angiopoietin-2; dexmedetomidine; endothelial injury; sepsis; vascular endothelial cadherin.

Figure 1

W/D weight ratio of lung tissue. The W/D ratios of the sham, CLP and Dex + CLP groups were measured. Each experiment was repeated six times. ^aP<0.05, compared with the sham group. ^bP<0.05, compared with the CLP group. CLP, cecal ligation and puncture; Dex, dexmedetomidine; W/D, wet/dry.

Figure 2

Dex significantly reduces the CLP-induced pulmonary edema as determined by H&E staining of rat lung tissue. Representative images showing the H&E staining of the upper lobe of right lung tissues of the rats in the sham, CLP and Dex + CLP groups. Arrows indicate the widened alveolar septum, infiltrated white blood cells, exuded edema fluid, as well as congestion in the CLP-treated rats compared with the sham rats. These alterations were markedly decreased in the Dex + CLP samples. CLP, cecal ligation and puncture; Dex, dexmedetomidine; H&E, hematoxylin and eosin.

Figure 3

Dex significantly decreases the CLP-induced elevation of the plasma Ang2 level and the Ang2/1 ratio. The plasma levels of Ang1 and 2 were detected by the corresponding ELISA kits. The ratio of Ang2/1 was calculated based on the levels of Ang1 and 2. Each experiment was repeated six times. ^aP<0.01, compared with the sham group; ^bP<0.01, compared with the CLP group. Ang, angiopoietin; CLP, cecal ligation and puncture; Dex, dexmedetomidine.

Figure 4

Dex alleviates the CLP-induced decrease in VE-cadherin protein expression. Protein samples of the rat middle lobe of right lung tissue from the sham, CLP and Dex + CLP groups were analyzed by western blotting with VE-cadherin antibody. GAPDH was used as a protein loading reference. The expression level of the protein was estimated by densitometry. The data are from three independent assays. ^aP<0.05, compared with the sham group. ^bP<0.05, compared with the CLP group. CLP, cecal ligation and puncture; Dex, dexmedetomidine; VE-cadherin, vascular endothelial cadherin.