摘要
Weaning piglets usually suffer from severe diarrhea(commonly known as postweaning diarrhea,PWD)along with intestinal motility disorder.Intestinal peristalsis is mainly regulated by the longitudinal muscle-myenteric plexus(LM-MP).To understand the relationship between intestinal LM-MP function and the development of PWD,we compared the intestinal electrical activity,and the transcriptional profile of the LM-MP between 21-day-old piglets(just weaned,n=7)and 24-day-old piglets(suffered the most severe weaning stress,n=7).The results showed that 24-day-old piglets exhibited different degrees of diarrhea.A significant increase in the slow-wave frequency in the ileum and colon was observed in 24-day-old piglets,while c-kit expression in the intestinal LM-MPs was significantly decreased,indicating that PWD caused by elevated slow-wave frequency may be associated with loss of c-kit.The real-time quantitative PCR(RT-q PCR)and enzyme-linked immunosorbent assay(ELISA)showed that intestinal LM-MPs in 24-day-old piglets may undergo inflammation and oxidative stress.Significant increases in 8-hydroxy-2′-deoxyguanosine and decreases in thioredoxin suggest that weaning may lead to DNA damage in the LM-MP of 24-day-old piglets.In addition,activating transcription factor 3 was significantly upregulated,indicating nerve damage in the LM-MP of 24-day-old piglets.The transcriptomic results showed that most of the differentially expressed genes in the ileal LM-MP after weaning were downregulated and closely related to the cell cycle process.Subsequent RT-q PCR analysis showed that the relative expression of p21 was upregulated,while the expression of cyclin A2,cyclin B1,and proliferating cell nuclear antigen was downregulated in the ileal and colonic LM-MP of 24-day-old piglets,suggesting that weaning may inhibit cell proliferation and cause G1/S cell cycle arrest in ileal and colonic LM-MP.In conclusion,weaning may lead to cell cycle arrest by causing DNA damage in the LM-MP,impairing intestinal motility regulation,and ultimately leading to diarrhea in piglets.
基金
supported by the National Natural Science Foundation of China(32130099)
the Scientific and Technological Project of Changsha City(kh2201234)。