Improvement effects of Tongxie yaofang on irritable bowel syndrome with diarrhea by regulating colonic TPH1,SERT and intestinal flora
OBJECTIVE To investigate the effects of Tongxie yaofang(TXYF)on the symptoms of rats with irritable bowel syndrome with diarrhea(IBS-D)by regulating colonic tryptophan hydroxylase 1(TPH1),serotonin transporter(SERT)and intestinal flora.METHODS Forty-two SD rats were randomly divided into control group(7 rats)and modeling group(35 rats).In modeling group,rat model of IBS-D was established by intragastrical administration of 0.45 g/L senna leaf solution[10 mL/(kg·d)]combined with chronic unpredictable stimulation.Thirty-five successfully modeled rats were randomly divided into model group,pinaverium bromide group[15 mg/(kg·d)]and TXYF low-dose,medium-dose and high-dose groups[3.75、7.5、15 g/(kg·d),calculated by crude drug],with 7 rats in each group.Each administration group was orally administered the corresponding drug,once a day,for 10 consecutive days.The general condition and weight changes of each group of rats were compared before modeling,after modeling and before administration,after the last drug intervention;the diarrhea index and visceral sensitivity were detected,and pathological changes of colon tissue were observed after modeling and before administration,after the last drug intervention.The level and expression of 5-hydroxytryptamine(5-HT),protein and mRNA expressions of TPH1 and SERT were determined in colon tissue.The diversity and structural changes of fecal intestinal flora of rats were analyzed.RESULTS There was no significant change in colon histopathology in each group.Compared with model group,the general condition of rats in each medication group improved.The daily body weight gain of rats was significantly increased,while diarrhea index,visceral sensitivity,the expressions of 5-HT and TPH1 in colon tissue were significantly decreased;SERT expression of colon tissue was significantly increased in TXYF medium-dose and high-dose groups(P<0.05 or P<0.01).The diarrhea index,colon TPH1 protein expression and colon 5-HT protein positive rate in the TXYF low-dose group decreased while the mRNA expression of SERT increased significantly(P<0.05).There was a dose-dependent trend in the effect of TXYF.Compared with model group,Chao1 index and Shannon index of the rats in TXYF high-dose group were significantly decreased(P<0.05 or P<0.01),the beneficial bacteria such as Firmicutes and Lactobacillus increased significantly,while the pathogenic bacteria such as Proteobacteria,Escherichia-Shigella and Rikenellaceae_RC9_gut_group decreased significantly(P<0.05 or P<0.01).CONCLUSIONS TXYF can decrease the level of 5-HT and improve intestinal flora disorder by inhibiting the expression of TPH1 and up-regulating the expression of SERT in colon tissue,thus promoting the symptoms of IBS-D rats.
Tongxie yaofangirritable bowel syndrome with diarrhea5-hydroxytryptaminetryptophan hydroxylase 1serotonin transporterintestinal flora