急性坏死性胰腺炎中NK-1R、NK-2R过表达与肠黏膜损伤的关系
Relationship between overexpression of NK-1R, NK-2R and intestinal mucosal damage in acute necrotizing pancreatitis.
作者信息
Shi Xin, Gao Nai-Rong, Guo Qing-Ming, Yang Yong-Jiu, Huo Ming-Dong, Hu Hao-Lin, Friess Helmut
机构信息
Department of General Surgery, Zhong-Da Hospital, Southeast University, Nanjing 210009, Jiangsu Province, China.
出版信息
World J Gastroenterol. 2003 Jan;9(1):160-4. doi: 10.3748/wjg.v9.i1.160.
AIM
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.
CONCLUSION
NK-1R and NK-2R contribute to disrupted neuropeptides loop balance, deteriorate intestinal damage, and are involved in pathophysiological changes in ANP.
目的
研究神经激肽-1受体（NK-1R）和神经激肽-2受体（NK-2R）在急性坏死性胰腺炎（ANP）大鼠回肠末端的表达，探讨二者表达与肠黏膜损伤的关系。
方法
将130只成年Sprague-Dawley大鼠随机分为两组：ANP组（n=80）采用逆行胰胆管内注射30 g.L(-1)牛磺胆酸钠诱导ANP模型；正常对照组（n=50）仅行剖腹术。分别于诱导后6 h、12 h、24 h和48 h处死ANP组和正常对照组大鼠。经空肠注射1.5 mCi放射性核素（99m）Tc-二乙三胺五乙酸（DTPA），测定诱导后6 h、12 h、24 h和48 h尿中（99m）Tc-DTPA含量，以研究肠黏膜通透性。然后取胰腺和肠组织进行病理检查。采用逆转录聚合酶链反应（RT-PCR）检测NK-1R和NK-2R的mRNA表达，采用蛋白质印迹法检测NK-1R和NK-2R的蛋白水平。
结果
ANP大鼠肠黏膜出现严重组织学损伤，ANP组尿中（99m）Tc-DTPA放射性显著增加。RT-PCR显示，与正常对照组相比，ANP大鼠回肠末端NK-1R和NK-2R的mRNA水平过度表达。蛋白质印迹法发现，ANP大鼠肠黏膜中NK-1R（增加14倍）和NK-2R（增加9倍）免疫反应性更强。此外，ANP大鼠中NK-1R的过度表达与黏膜病理评分（r=0.77，P<0.01）和肠通透性（r=0.68，P<0.01）相关。
结论
NK-1R和NK-2R导致神经肽环路平衡破坏，加重肠损伤，参与ANP的病理生理变化。
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