Antinociceptive effect of VSL#3 on visceral hypersensitivity in a rat model of irritable bowel syndrome: a possible action through nitric oxide pathway and enhance barrier function.
Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel function. There are increasing evidences suggested that VSL#3 probiotics therapy has been recognized as an effective method to relieve IBS-induced symptoms. The aim of this study was to examine the effects of VSL#3 probiotics on visceral hypersensitivity (VH), nitric oxide (NO), fecal character, colonic epithelium permeability, and tight junction protein expression. IBS model was induced by intracolonic instillation of 4% acetic acid and restraint stress in rats. After subsidence of inflammation on the seventh experimental day, the rats were subjected to rectal distension, and then the abdominal withdrawal reflex and the number of fecal output were measured, respectively. Also, colonic permeability to Evans blue was measured in vivo, and tight junction protein expression was studied by immunohistochemistry and immunoblotting method. Rats had been pretreated with VSL#3 or aminoguanidine (NOS inhibitor) or VSL#3+ aminoguanidine before measurements. The rats at placebo group showed hypersensitive response to rectal distension (P < 0.05) and defecated more stools than control rats (P < 0.05), whereas VSL#3 treatment significantly attenuated VH and effectively reduced defecation. Aminoguanidine reduced the protective effects of VSL#3 on VH. A pronounced increase in epithelial permeability and decreased expression of tight junction proteins (occludin, ZO-1) in placebo group were prevented by VSL#3, but not aminoguanidine. VSL#3 treatment reduce the hypersensitivity, defecation, colonic permeability and increase the expression of tight junction proteins (occludin, ZO-1). As the part of this effect was lowered by NOS inhibitor, NO might play a role in the protective effect of VSL#3 to some extent.
Department of Gastroenterology, First Affiliated Hospital, China Medical University, Shenyang City, Liaoning Province, China.
Cong
C
Dai
Stefano
S
Guandalini
De-Hui
DH
Zhao
Min
M
Jiang
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000503:physiopathology; D043183:Irritable Bowel Syndrome / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D009569:Nitric Oxide / Q000378:metabolism; D062793:Occludin; D059408:Pain Management; D010539:Permeability; D010750:Phosphoproteins / Q000096:biosynthesis; D019936:Probiotics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000187:drug effects*; D062826:Zonula Occludens-1 Protein
D006146:Guanidines; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D009569:Nitric Oxide; C004479:pimagedine