Dioscin ameliorates slow transit constipation in mice by up-regulation of the BMP۲ secreted by muscularis macrophages

سال انتشار: 1401
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 116

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شناسه ملی سند علمی:

JR_IJBMS-25-9_013

تاریخ نمایه سازی: 20 شهریور 1401

چکیده مقاله:

Objective(s): The loss of enteric neurons has been shown to be a major cause of slow transit constipation (STC). Gut microbiota and muscularis macrophages (MMs) are associated with the enteric nervous system (ENS) development and gastrointestinal (GI) motility. This study aimed to investigate whether Dioscin (DIO) increased GI motility and inhibited neuron loss by modulating gut microbiota profile, improving inflammation in the ENS microenvironment.Materials and Methods: The STC model was established by loperamide. The alteration of the gut microbiota was analyzed by ۱۶S rDNA sequencing. The longitudinal muscle and myenteric plexus (LMMP) from the colon were prepared for flow cytometry, immunofluorescence, western blot, and qRT-PCR. Results: DIO increased the stool number, stool water content and shortened whole gut transit time, helped to recover the gut microbial diversity and microbiota community structure, and increased the abundance of Muribaculaceae in STC mice. Compared with the STC group, the number of MMs and the level of the iNOS, IL-۶, and TNFα genes were significantly decreased following DIO treatment. Moreover, DIO may increase the number of HuC/D+ neurons per ganglion by up-regulating the BMP۲ secreted by MMs and activating the BMP۲/p-Smad۱/۵/۹ signaling pathway. Furthermore, the level of excitatory neurotransmitter AchE in colon tissues exhibited a substantial increase in the DIO group. However, the level of inhibitory neurotransmitter VIP was markedly decreased. Conclusion: Our results provide that DIO increases GI motility and inhibits neuron loss by modulating gut microbiota profile, improving inflammation in the ENS microenvironment and up-regulating the BMP۲ secreted by MMs.

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نویسندگان

Bingbing Ren

Department of Pediatric Surgery, General Hospital, Tianjin Medical University, Tianjin, China

Siqi Fu

Department of Pediatric Surgery, General Hospital, Tianjin Medical University, Tianjin, China

Yong Liu

Department of Pediatric Surgery, General Hospital, Tianjin Medical University, Tianjin, China

JianYu Kang

Department of Pediatric Surgery, General Hospital, Tianjin Medical University, Tianjin, China

Bo Wang

Department of Pediatric Surgery, General Hospital, Tianjin Medical University, Tianjin, China

ZhiWei Yao

Department of Pediatric Surgery, General Hospital, Tianjin Medical University, Tianjin, China

Hao Wang

Department of General Surgery, General Hospital, Tianjin Medical University, Tianjin, China

DaQing Sun

Department of Pediatric Surgery, General Hospital, Tianjin Medical University, Tianjin, China

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