Relationship between overexpression of NK-1R, NK-2R and intestinal mucosal damage in acute necrotizing pancreatitis

AlM: To study the expression of neurokinin-1 receptor (NK-1R) and neurokinin-2 receptor (NK-2R) in distal ileum ofacute necrotizing pancreatitis (ANP) and to evaluate therelationship between expression of these two receptors andintestinal mucosal damage.METHODS: A total of 130 adult Sprague-Dawley rats wererandomly divided into two groups: the rats in ANP group(n＝80) were induced by the retrograde intraductal infusionof 30 g@L-1 sodium taurocholate. And the rats in normal controlgroup (n＝50) received laparotomy only. Sacrifices weremade 6 h, 12 h, 24 h and 48 h later in ANP and normalcontrol group after induction respectively. Intestinal mucosalpermeability was studied by intrajejunal injection of 1.SmCiradioactive isotope 99mTc-diethlene triamine pentacetic acid(DTPA) and the radioactivity of 99mTc-DTPA content in urinewas measured 6 h, 12 h, 24 h and 48 h after induction.Then the pancreas and intestine were prepared forpathology. Reverse transcription polymerase chain reaction(RT-PCR) was used to determine the mRNA expression ofNK-1R and NK-2R, and Western blot was used to investigatethe protein level of NK-1R and NK-2R.RESULTS: In ANP rats, serious histologic damages inintestinal mucosa were observed, and the radioactivity of99mTc-DTPA in urine increased significantly in the ANP group.RT-PCR revealed that NK-1R and NK-2R mRNA level wasoverexpressed in the distal ileum of ANP as compared withthe normal control group. Western blot discovered strongerNK-1R (14-fold increase) and NK-2R (9-fold increase)immunoreactivity in the intestinal mucosa of ANP rats.Moreover, the overexpression of NK-1R was associated withmucosal pathological score (r＝0.77,P＜0.01) and intestinalpermeability (r＝0.68, P＜0.01) in ANP rats.CONCLUSION: NK-1R and NK-2R contribute to disruptedneuropeptides loop balance, deteriorate intestinal damage,and are involved in pathophysiological changes in ANP.