APETx2 regulates intestinal motility and visceral sensitivity in post-infectious irritable bowel syndrome mice through 5-HT signalling pathway.

OBJECTIVES: To investigate whether APETx2, a potent and selective inhibitor of ASIC3, regulates intestinal motility and visceral sensitivity in post-infectious irritable bowel syndrome (PI-IBS) mice through the 5-HT signalling pathway. METHODS: The PI-IBS model was established by Trichinella spiralis infection of NIH mice. APETx2(120 µg/kg) was administrated to PI-IBS mice by intraperitoneal injection once a day, lasting for 7 days. The gastrointestinal function of mice was assessed by the time of the first dark stool and the number of pellets defecated within 2 h. The visceral sensitivity was tested via abdominal withdrawal reflex. The protein levels of 5-HT and CRF in colon tissues were detected by immunohistochemistry. The changes in serum 5-HT and colon CRF contents were detected by ELISA. The mRNA levels of colon 5-HT4R and CRF were detected by RT-qPCR. The protein levels of colon 5-HT4R and dorsal root ganglion (DRG) ASIC3 were detected by Western blotting. KEY FINDINGS: The results indicated that APETx2 could markedly improve gastrointestinal function and visceral sensitivity in mice. Moreover, APETx2 could reduce the expression level of ASIC3 protein in the DRG of PI-IBS mice. APETx2 could increase the expression levels of 5-HT in serum and colon, CRF and 5-HT4R in the colon, and 5-HT4R in brain tissue in PI-IBS mice. CONCLUSIONS: APETx2 can improve visceral sensitivity and intestinal motility in PI-IBS through 5-HT signalling pathway.

Clinical Effect of Modified Jichuanjian on Senile Patients with Slow Transit Constipation of Spleen-kidney Yang Deficiency Syndrome and Effect on Brain-gut Peptide / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of modified Jichuanjian on senile patients with slow transit constipation of spleen-kidney yang deficiency syndrome and the influence on brain-gut peptide. MethodA total of 150 senile patients with slow transit constipation were randomized into control group （75 cases） and observation group （75 cases） with the random number table method. The observation group was given modified Jichuanjian （oral， 1 dose/day， 4 weeks）， and the control group was treated with Biantong Capsules （oral， 3 capsules/time， twice/day， 4 weeks）. Data before and after treatment were recorded， including the score of major constipation symptoms， score of Patient Assessment of Constipation Quality of Life （PAC-QOL）， TCM syndrome score， spontaneous complete bowel movements （SCBM）， colonic transit test， serum 5-hydroxytryptamine （5-HT）， 5-HT 4 receptor （5-HT4R）， somatostatin （SS）， and vasoactive intestinal peptide （VIP）， and recurrence. ResultThe total effective rate of the observation group was 93.06% （67/72）， as compared with the 74.65% （53/71） in the control group （χ2=8.974 6， P<0.01）. After treatment， the scores of major constipation symptoms， scores of four dimensions of PAC-QOL， total score of PAC-QOL， and TCM syndrome score were lower than those before treatment in the two groups （P<0.01）， and lower in the observation group than in the control group （P<0.01）. The SCBM in the observation group were more than those in the control group at the 2nd， 3rd， 4th weeks after treatment （P<0.01）. The proportions of residual markers at 24， 48， 72 h after treatment were smaller than those before treatment in the two groups （P<0.01）， and smaller in the observation group than in the control group （P<0.01）. After treatment， the levels of serum 5-HT and 5-HT4R were higher （P<0.01） and the levels of serum SS and VIP were lower （P<0.01） than those before treatment in the two groups. In addition， the levels of serum 5-HT and 5-HT4R in the observation group were higher （P<0.01） and the levels of serum SS and VIP were lower （P<0.01） in the observation group than in the control group. The recurrence in the observation group was 29.85% （20/67） in comparison with the 58.49% （31/53） in the control group （χ2=9.932 4， P<0.01）. ConclusionModified Jichuanjian is effective for senile patients with slow transit constipation of spleen-kidney yang deficiency syndrome， which can alleviate clinical symptoms， improve quality of life， regulate the level of serum brain-gut peptide， improve the colonic transit function， increase SCBM， and reduce the recurrence.

Clinical Efficacy of Modified Qilang Prescription in Treatment of Drug-dependent Constipation with Qi and Yin Deficiency and Its Effect on MTL， VIP， 5-HT， and 5-HT4R in Peripheral Blood / 中国实验方剂学杂志

Objective:To investigate the curative efficacy of modified Qilang prescription on drug-dependent constipation with Qi and Yin deficiency and the effects on serum vasoactive intestinal peptide （VIP）， motilin （MTL）， 5-hydroxytryptamine （5-HT）， and 5-hydroxytryptamine 4 receptor （5-HT4R）. Method:A total of 160 patients diagnosed with drug-dependent constipation were randomly divided into a treatment group （<italic>n</italic>=80， Qilang prescription） and a control group （<italic>n</italic>=80， lactulose oral solution）. The treatment lasted for eight weeks. Changes in clinical symptoms， traditional Chinese medicine （TCM） syndrome， and serum VIP， MTL， 5-HT， and 5-HT4R before and after treatment were observed. The clinical efficacies of the two groups were compared. An eight-week follow-up was carried out for the observation of recurrent rate and TCM syndrome. Result:The overall response rate of the treatment group （90.91%） was higher than that （75.00%） of the control group<italic> </italic>（<italic>Z</italic>=-6.514，<italic>P</italic><0.05）. There was no significant difference in serum VIP， MTL， 5-HT， and 5-HT4R between the two groups before treatment. After treatment for eight weeks， both groups showed reduced serum VIP level as compared with those before treatment， and the treatment group was inferior to the control group （<italic>P</italic><0.05）. The serum MTL levels of the two groups were both higher than those before treatment （<italic>P</italic><0.05）， and the treatment group was superior to the control group （<italic>P</italic><0.05）. After treatment， the level of 5-HT in the treatment group was higher than that in the control group （<italic>P</italic><0.05）. The post-treatment 5-HT4R level in the treatment group slightly increased （<italic>P</italic><0.05）， but no significant difference in 5-HT4R levels between the two groups after treatment was observed. During the eight-week follow-up， the recurrence rate in the treatment group was significantly lower than that in the control group at the 2nd and 4th weeks （<italic>P</italic><0.05）. There was no significant difference in the recurrence rate between the treatment group ［57.14% （40/70）］ and the control group ［64.81% （35/54）］ after eight weeks. Conclusion:Modified Qilang prescription was superior to lactulose in the short- and mid-term efficacy on drug-dependent constipation with Qi and Yin deficiency. No significant difference in the long-term efficacy was observed. The underlying therapeutic mechanism might be related to the regulation of serum VIP， MTL， 5-HT， and 5-HT4R levels.