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. 2012 Oct 23:10:219.
doi: 10.1186/1477-7819-10-219.

The role of the 5-hydroxytryptamine pathway in reflux-induced esophageal mucosal injury in rats

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The role of the 5-hydroxytryptamine pathway in reflux-induced esophageal mucosal injury in rats

Lingrong Yang et al. World J Surg Oncol. .

Abstract

Background: Dysfunction of the 5-hydroxytryptamine (5-HT) signaling pathway can lead to gastrointestinal motility and secretion abnormalities and to visceral hypersensitivity. The aim of this study is to investigate the role of 5-HT in reflux-induced esophageal mucosal injury.

Methods: Fifty 8-week-old male Sprague-Dawley (SD) rats were randomly divided into a gastroesophageal reflux (GER) model group (30 rats) and a sham surgery control group (20 rats). Four weeks after surgery, the esophageal mucosa was collected for histological evaluation, 5-HT concentrations, and 5-HT selective reuptake transporter (SERT) mRNA and 5-HT4 receptor (5-HT4R) protein expressions.

Results: Twenty-seven rats in the GER model group survived, and three rats died. Histologically, in the GER model group, 20 rats had reflux esophagitis (RE group), and 7 rats had non-erosive reflux disease (NERD group). The 5-HT levels in the esophageal tissue from the RE group were significantly higher than those from the control and NERD groups. Both the RE and NERD groups showed significant increases in SERT mRNA expression of the esophageal mucosa than that of the controls, and the SERT mRNA level in the RE group was significantly higher than that in the NERD group. The 5-HT4R protein level of the esophageal mucosa in the RE group was significantly lower than that in the controls and the NERD group.

Conclusions: We conclude that a 5-HT signaling pathway disorder could be a major factor in the pathogenesis of GER and RE.

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Figures

Figure 1
Figure 1
Gross findings of esophageal mucosa in GER rat (A) and sham-operated controls (B). Normal macroscopic esophageal mucosa is shown in A. The presence of gross inflammation is shown in B, such as esophageal mucosal congestion or erosion.
Figure 2
Figure 2
Histological assessment of the esophageal mucosa (hematoxylin and eosin ×200) from sham operated rats (A) and GER model rats (B, C). Normal esophageal mucosa is shown in A (controls). The absence of esophageal mucosal inflammation is shown in B (NERD). Basal layer thickening, vascular congestion, and infiltration of inflammatory cells, such as eosinophils, are shown in C (reflux esophagitis, RE).
Figure 3
Figure 3
Serotonin (5-HT) content (ng/ml) in the esophageal tissue of rats with reflux esophagitis (RE) and in NERD rats. 5-HT levels were significantly higher in the esophageal tissue of rats with RE compared to controls (*P < 0.05). 5-HT content was significantly lower in the esophageal tissue of NERD rats than those with RE (#P < 0.05).
Figure 4
Figure 4
Relative expression of serotonin reuptake transporter (SERT) mRNA levels in the esophageal tissue of rats with reflux esophagitis (RE) and NERD rats. The results are expressed as Δct. A significantly higher level of SERT mRNA was detected in samples from both RE rats and NERD rats compared to controls (*P < 0.01), while SERT transcript levels were significantly increased in the esophageal tissue of rats with RE compared to NERD rats (#P < 0.01).
Figure 5
Figure 5
The protein expression of 5-HT4R in the esophageal tissue in rats with RE and in NERD rats as detected by Western blots. Representative Western blots of 5-HT4R in each group are shown at the top, with GAPDH expression used as a control (A). The results are expressed the ratio of 5-HT4R to GAPDH for immunoblots. Note that 5-HT4R expression is significantly downregulated in RE rats compared to NERD rats and controls. *P < 0.01 (B).

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