关键词: 肠易激综合征, 酸敏感离子通道, 酸敏感离子通道阻滞剂, APETx2, 母婴分离, 内脏敏感性

Abstract: Objective To investigate the effect of fecal bacterial transplantation on visceral sensitivity of rats with irritable bowel syndrome (IBS) induced by neonatal maternal separation (NMS), and the role of acid-sensitive ion channel 3 (ASIC3) inhibitor APETx2 on visceral sensitivity in the development of IBS. Methods Ten pregnant SD rats were taken, and the IBS model was constructed by NMS after the birth. The feces of the successful model rats were collected to make fecal microbiota solution. Eighteen healthy male SD rats were randomly divided into the normal control group (Con group), the neonatal maternal separation group (NMS group) and the NMS+APETx2 treatment group, 6 rats for each group. The NMS group and NMS+APETx2 group were given ABX-water continuously for 5 days to establish the pseudo-aseptic model rats, then NMS rats were given intragastric administration of fecal microbiota solution (1.6 mL/kg). The Con group was given the equal volume of normal saline consecutively for 5 days, once a day. After the gavage, the NMS+APETx2 group was given 100 μg/kg APETx2 continuous intraperitoneal injection for 7 days, once a day. The ink movement test was used to determine the intestinal transit rate, and the visceral sensitivity was evaluated after colorectal balloon distention (CRD) stimulation. Immunohistochemistry was performed to detect the localization of ASIC3 and c-kit, and the changes of morphology and number of Cajal cells were observed. Results Compared with the Con group, the NMS group had slower intestinal transit rate, increased visceral sensitivity with the higher abdominal withdrawal reflex (AWR) scores, promoted expression of ASIC3 and c-kit in colon tissue, and morphological changes of ICC cells. Compared with the NMS group, there were significantly accelerated intestinal transit rate, decreased sensitivity of the intestine with the lower AWR scores, suppressed ASIC3 and c kit expression in colon tissue, and the morphology tended to be normal and the number of ICC was reduced in the NMS+ APETx2 group. Conclusion Fecal bacteria transplantation from IBS can induce visceral hypersensitivity and reduce intestinal transmission. APETx2 can alleviate visceral sensitivity and intestinal transmission, which may be related to the inhibition of ASIC3 expression and down-regulation of the c-kit signal associated Cajal cells.

Key words: irritable bowel syndrome, acid sensing ion channels, acid sensing ion channel blockers, APETx2, neonatal maternal separation, intestinal sensitivity