The Effect Of Glycyrrhizin On Visceral Hypersensitivity Model Rats And 5-HT Signaling Pathway

Irritable Bowel Syndrome(IBS)is one of the common functional gastrointestinal disorders.IBS is primarily characterized by chronic abdominal pain or discomfort,and altered bowel habits in the absence of evidence of organic diseases.Accumulating evidences demonstrate that it is related to visceral hypersensitivity.Among these,visceral hypersensitivity could be thought as a biological marker of the syndrome.Thus,the aim of our present study was to investigate the effect of GA on visceral hypersensitivity in rats and its underlying action mechanisms.1.Multiple Stress Protocol Rats were subjected to 21 consecutive days.5 random stressors,abrosia,fasting water,water avoidance stress,cold restraint stress and forced swimming stress.Then,using general state(appearance behavior score,weight changes),psychological state(sucrose consumption test),the gut feeling(pain threshold pressure,abdominal withdrawal reflex)to appraisal the model.The results showed that the model was success.2.From day 22,model rats were orally administrated GA(12.5,25 and 50mg/kg)and Pinaverium(15mg/kg)for 7 days,respectively.The results showed that the GA significantly increased rat behavioral model score(P<0.05),sugar partial addicted scores(P<0.01)and threshold pressure(P<0.01).On 20 mmHg,40 mmHg,60 mmHg,80 mmHg,compared with the normal group,GA significantly reduced the abdominal withdrawal reflex scores of rat model(P<0.05).Compared with the model group,the levels of SS,SP,CGRP,VIP was significantly increased(P<0.05);compared with the model group,GA significantly decreased the level of SS,SP,CGRP,VIP in serum(P<0.05).In conclusion,GA ameliorated the general state,psychological behavior,gut feeling in visceral hypersensitivity rats and regulated the levels of gastrointestinal hormone in serum.3.ELISA and Real-time quantitative PCR were used to measure the levels of protein and mRNA of 5-HT pathway.ELISA study showed that GA treatment significantly reduced the 5-HT concentration,5HT3R,5HT4R and TPH-1 concentrations(P<0.05,P<0.01),and improved 5-HT conversion rates(P<0.05),from the distal colon compared to the saline group.Real-time quantitative PCR showed that GA treatment substantially reduced mRNA levels of 5HT3R,5HT4R and TPH-1 from the distal colon conpared with thesaline group.In summary,the present study explored treatment of GA on visceral hypersensitivity in rats,and studied the therapeutic effect which may be related to 5-HT signaling pathway.This study not only provided experimental evidence for clinical efficacy,but also clarified the mechanism of traditional Chinese medicine for the treatment of IBS.