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Mechanisms of Probiotic VSL#3 in a Rat Model of Visceral Hypersensitivity Involves the Mast Cell-PAR2-TRPV1 Pathway

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Abstract

Background

Mast cells (MCs), PAR2 and TRPV1, play a key role in the regulation of visceral pain. Several studies have found that probiotics regulate visceral sensitivity.

Aims

The purpose of the current study was to explore the role of MC-PAR2-TRPV1 in VH and the mechanism of VSL#3 in a rat model of VH.

Methods

A total of 64 rats were randomly divided into eight groups: Control VH, VH + ketotifen, VH + FSLLRY-NH2, VH + SB366791, VH + VSL#3, VH + VSL#3 + capsaicin, and VH + VSL#3 + SLIGRL-NH2. The rat model of VH was induced by acetic acid enema and the partial limb restraint method. VH was assessed by the abdominal withdrawal reflex score. MCs in colonic tissue were detected by the toluidine blue staining assay. The expression of PAR2 and TRPV1 in DRGs (L6–S1) was measured by immunohistochemistry and Western blotting.

Results

The established VH was abolished by treatment with ketotifen, a mast cell stabilizer FSLLRY-NH2, a PAR2 antagonist SB366791 a TRPV1 antagonist, and probiotic VSL#3 in rats. The administration of ketotifen or probiotic VSL#3 caused a decrease in mast cell number in the colon and decreased PAR2 and TRPV1 expression in DRGs. Intrathecal injection of FSLLRY-NH2 or SB366791 caused decreased expression of PAR2 and/or TRPV1 in DRGs in VH rats. SLIGRL-NH2, a PAR2 agonist, and capsaicin, a TRPV1 agonist, blocked the effects of probiotic VSL#3.

Conclusions

The probiotic VSL#3 decreases VH in rat model of VH. The mechanism may be related with the mast cell-PAR2-TRPV1 signaling pathway.

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Funding

This research was supported by the National Nature Science Foundation of China (No. 81300273), the Fund for Scientific Research of The First Hospital of China Medical University (No. FSFH2O1702) and the Liaoning Science and Technology Foundation (No. 20170541052).

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Authors and Affiliations

  1. Department of Gastroenterology, First Affiliated Hospital, China Medical University, No. 92 of Beier Road, Heping District, Shenyang City, 110001, Liaoning Province, China

    Ying-Jie Li, Cong Dai & Min Jiang

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  1. Ying-Jie Li
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Correspondence to Cong Dai or Min Jiang.

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10620_2018_5416_MOESM1_ESM.tif

HE staining of colonic segments A. Control group B. VH group C. VH + ketotifen group D. VH + FSLLRY-NH2 group E. VH + SB366791 group F. VH + VSL#3 + SLIGRL-NH2 group G. VH + VSL#3 + capsaicin group H. VH + VSL#3 group; n = 8 per group. Scale bar, 200 μm (TIFF 8219 kb)

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Li, YJ., Dai, C. & Jiang, M. Mechanisms of Probiotic VSL#3 in a Rat Model of Visceral Hypersensitivity Involves the Mast Cell-PAR2-TRPV1 Pathway. Dig Dis Sci 64, 1182–1192 (2019). https://doi.org/10.1007/s10620-018-5416-6

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