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Therapeutic effect of protease-activated receptor 2 agonist SLIGRL-NH2 on loperamide-induced Sprague-Dawley rat constipation model and the related mechanism

Authors Zhang Y, Ge T, Xiang P, Mao H, Tang S, Li A, Lin L, Wei Y

Received 22 December 2017

Accepted for publication 24 April 2018

Published 1 August 2018 Volume 2018:12 Pages 2403—2411


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Anastasios Lymperopoulos

Yonggang Zhang,1 Tingrui Ge,1 Ping Xiang,1 Haibing Mao,1 Shumin Tang,1 Aimin Li,2 Lin Lin,3 Yinting Wei4

1Department of Colorectal Surgery, The First People’s Hospital of Lianyungang, Lianyungang 222002, China; 2Department of Neurosurgery, The First People’s Hospital of Lianyungang, Lianyungang 222002, China; 3Department of Gastroenterology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; 4Department of Gastroenterology, Lianyungang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Lianyungang 222000, China

Purpose: To investigate the therapeutic effects of protease-activated receptor 2 (PAR-2) agonist SLIGRL-NH2 on loperamide-induced Sprague-Dawley (SD) rat constipation animal models.
Materials and methods: Loperamide was injected subcutaneously to induce constipation twice a day for 3 days. SD rats (n = 30) were randomly divided into five groups: non-constipation group (control, n = 6), constipation group (constipation, n = 6), constipation + SLIGRL-NH2 low-dosage group (SLIGRL-NH2 low, n=6), constipation + SLIGRL-NH2 high-dosage group (SLIGRL-NH2 high, n = 6), and constipation + prucalopride (positive control, n = 6). The SLIGRL-NH2 low group and SLIGRL-NH2 high group were administered with 2.5 μmol/kg and 5 μmol/kg SLIGRL-NH2, respectively, and the prucalopride group received 2 mg/kg prucalopride. The control and constipation group received 1× PBS under the same pattern. SLIGRL-NH2 and prucalopride were orally administrated once daily for 7 days. On the final day of oral administration, food intake, water intake, the number of stool pellets, weight, and fecal water content was calculated; moreover, the colons of rats in different groups were collected and histological features were examined by hematoxylin and eosin staining; furthermore, the expression of anoctamin-1 was determined by Immunohistochemical methods, and the expressions of c-kit and PAR-2 were examined using real-time quantitative polymerase chain reaction and Western blot methods; finally, the expressions of neurotransmitter vasoactive intestinal peptide (VIP) and substance P (SP) were examined using enzyme-linked immunosorbent assay methods.
Results: The feeding and excretion behaviors, intestinal transit ratio, and the histological feature of the colon in the constipated rats were all improved by SLIGRL-NH2 treatment; moreover, SLIGRL-NH2 treatment induced significant increase in the expression of PAR-2 and also increased number of interstitial Cajal cells. Furthermore, SLIGRL-NH2 also decreased the contents of the inhibitory neurotransmitter VIP and increased the expression of the excitatory neurotransmitter SP. High dose of SLIGRL-NH2 has shown similar anti-constipation effects as prucalopride.
Conclusion: These results suggested that SLIGRL-NH2 can enhance gastrointestinal transit and alleviate in rats with loperamide-induced constipation.

Keywords: constipation, PAR-2, SLIGRL-NH2, loperamide, interstitial Cajal cells

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