Relationship between overexpression of NK-1R, NK-2R and intestinal mucosal damage in acute necrotizing pancreatitis.
OBJECTIVE
To study the expression of neurokinin-1 receptor (NK-1R) and neurokinin-2 receptor (NK-2R) in distal ileum of acute necrotizing pancreatitis (ANP) and to evaluate the relationship between expression of these two receptors and intestinal mucosal damage.


METHODS
A total of 130 adult Sprague-Dawley rats were randomly divided into two groups: the rats in ANP group (n=80) were induced by the retrograde intraductal infusion of 30 g.L(-1) sodium taurocholate. And the rats in normal control group (n=50) received laparotomy only. Sacrifices were made 6 h, 12 h, 24 h and 48 h later in ANP and normal control group after induction respectively. Intestinal mucosal permeability was studied by intrajejunal injection of 1.5 mCi radioactive isotope (99m)Tc-diethlene triamine pentacetic acid (DTPA) and the radioactivity of (99m)Tc-DTPA content in urine was measured 6 h, 12 h, 24 h and 48 h after induction. Then the pancreas and intestine were prepared for pathology. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the mRNA expression of NK-1R and NK-2R, and Western blot was used to investigate the protein level of NK-1R and NK-2R.


RESULTS
In ANP rats, serious histologic damages in intestinal mucosa were observed, and the radioactivity of (99m)Tc-DTPA in urine increased significantly in the ANP group. RT-PCR revealed that NK-1R and NK-2R mRNA level was overexpressed in the distal ileum of ANP as compared with the normal control group. Western blot discovered stronger NK-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 with mucosal pathological score (r=0.77, P<0.01) and intestinal permeability (r=0.68, P<0.01) in ANP rats.


CONCLUSIONS
NK-1R and NK-2R contribute to disrupted neuropeptides loop balance, deteriorate intestinal damage, and are involved in pathophysiological changes in ANP.
Shi
Xin
X
Department of General Surgery, Zhong-Da Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China. shixined@hotmail.com
Gao
Nai-Rong
NR
Guo
Qing-Ming
QM
Yang
Yong-Jiu
YJ
Huo
Ming-Dong
MD
Hu
Hao-Lin
HL
Friess
Helmut
H
D000681:Amylases / Q000097:blood; D000818:Animals; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D019283:Pancreatitis, Acute Necrotizing / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000235:genetics / Q000378:metabolism*; D013223:Statistics as Topic
D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D000681:Amylases