Microsomal Prostaglandin E Synthase-1 Plays a Critical Role in Long-term Motility Dysfunction after Bowel Obstruction

作者：Lin, You-Min; Fu, Yu; Hegde, Shrilakshmi; Tang, Yanbo; Radhakrishnan, Ravi; Shi, Xuan-Zheng^*

来源：Scientific Reports, 2018, 8(1): 8831.

DOI：10.1038/s41598-018-27230-6

• CHRONIC INTESTINAL PSEUDOOBSTRUCTION
• PERISTALTIC REFLEX
• COLONIC MOTILITY
• PAIN
• PROGNOSIS
• DIAGNOSIS
• STENOSIS
• DISEASE
• SURGERY
• LIFE

Motility dysfunction is present not only during bowel obstruction (BO), but after obstruction is resolved. Previous studies found that lumen distension associated mechano-transcription of COX-2 and production of PGE(2) in gut smooth muscle cells (SMC) account for motility dysfunction during obstruction. We hypothesized that PGE2 may exert autocrine effect in SMC to induce microsomal prostaglandin E synthase-1 (mPGES-1), which contributes to motility dysfunction after obstruction is resolved. Partial colon obstruction was induced in rats with an obstruction band, which was released 7 days later. Rats were further studied in the post-BO state. Circular muscle contractility of the mid colon (previously distended during obstruction) remained suppressed, and colon transit was impaired in the post-BO state. The COX-2, mPGES-1, and PGE2 levels were all increased in the distended bowel during obstruction. However, after obstruction was resolved, COX-2 expression returned to normal, whereas mPGES-1 and PGE2 levels remained increased. Expression of mPGES-1 in colon SMC was inducible by stretch or PGE2. Administration of mPGES-1 inhibitor Cay 10526 either before or after the release of obstruction normalized PGE2 levels and improved motility in the post-BO rats. In conclusion, mPGES-1 plays a critical role in the continuous suppression of motor function in the post-BO state.

• 出版日期2018-6-11
• 单位广西大学