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

Lingrong Yang123, Haifang Cai124, Jinfa Tou12, Weizhong Gu12, Xiaoli Shu12, Ting Zhang12, Xi Yang12, Zheng Shen12 and Mizu Jiang12*

Author Affiliations

1 Department of Gastroenterology, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China

2 Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou, 310003, People’s Republic of China

3 The present address: The Third People's Hospital of Chengdu, Chengdu, 610031, People’s Republic of China

4 The present address: The Central Hospital of Lishui City, Lishui, 323000, People’s Republic of China

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World Journal of Surgical Oncology 2012, 10:219  doi:10.1186/1477-7819-10-219

Published: 23 October 2012



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.


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.


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.


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

5-hydroxytryptamine; Gastroesophageal reflux; Reflux esophagitis; 5-HT selective reuptake transporter; 5-hydroxytryptamine 4 receptor