Al-Mufti R A, Williamson R C, Mathie R T
Department of Gastrointestinal Surgery, Hammersmith Hospital, Imperial College School of Medicine, London, UK.
Gut. 1998 Oct;43(4):564-70. doi: 10.1136/gut.43.4.564.
Overproduction of nitric oxide (NO) via induction of the inducible NO synthase (iNOS) is an important factor in the haemodynamic disturbances of several inflammatory states.
To identify the role of NO in a caerulein induced model of acute pancreatitis in the rat.
Arterial blood pressure and plasma NO metabolites were measured at zero and seven hours in adult male Wistar rats administered caerulein (n=10) or saline (n=10). Pancreatic activity of NOS (inducible and constitutive) was assayed biochemically. The pancreatic expression and cellular localisation of NOS and nitrotyrosine (a marker of peroxynitrite induced oxidative tissue damage) were characterised immunohistochemically.
Compared with controls at seven hours, the pancreatitis group displayed raised plasma NO metabolites (mean (SEM) 70.2 (5.9) versus 22.7 (2.2) micromol/l, p<0.0001) and reduced mean arterial blood pressure (88.7 (4.6) versus 112.8 (4.1) mm Hg, p=0.008). There was notable iNOS activity in the pancreatitis group (3.1 (0.34) versus 0.1 (0.01) pmol/mg protein/min, p<0.0001) with reduced constitutive NOS activity (0.62 (0.12) versus 0.96 (0.08) pmol/mg protein/min, p=0.031). The increased expression of iNOS was mainly localised within vascular smooth muscle cells (p=0.003 versus controls), with positive perivascular staining for nitrotyrosine (p=0.0012 versus controls).
In this experimental model of acute pancreatitis, iNOS induction and oxidative tissue damage in the pancreas is associated with raised systemic NO and arterial hypotension. Excess production of NO arising from the inducible NO synthase may be an important factor in the systemic and local haemodynamic disturbances associated with acute pancreatitis.
通过诱导型一氧化氮合酶（iNOS）过度产生一氧化氮（NO）是多种炎症状态下血流动力学紊乱的一个重要因素。
确定NO在大鼠雨蛙肽诱导的急性胰腺炎模型中的作用。
在给予雨蛙肽（n = 10）或生理盐水（n = 10）的成年雄性Wistar大鼠中，于0小时和7小时测量动脉血压和血浆NO代谢产物。对NOS（诱导型和组成型）的胰腺活性进行生化检测。通过免疫组织化学对NOS和硝基酪氨酸（过氧亚硝酸盐诱导的氧化组织损伤的标志物）的胰腺表达和细胞定位进行表征。
与7小时时的对照组相比，胰腺炎组血浆NO代谢产物升高（均值（标准误）70.2（5.9）对22.7（2.2）μmol/L，p<0.0001），平均动脉血压降低（88.7（4.6）对112.8（4.1）mmHg，p = 0.008）。胰腺炎组有显著的iNOS活性（3.1（0.34）对0.1（0.01）pmol/mg蛋白/分钟，p<0.0001），组成型NOS活性降低（0.62（0.12）对0.96（0.08）pmol/mg蛋白/分钟，p = 0.031）。iNOS表达增加主要定位于血管平滑肌细胞（与对照组相比p = 0.003），血管周围硝基酪氨酸染色呈阳性（与对照组相比p = 0.0012）。
在这个急性胰腺炎实验模型中，胰腺中iNOS的诱导和氧化组织损伤与全身NO升高和动脉低血压有关。诱导型一氧化氮合酶产生的过量NO可能是与急性胰腺炎相关的全身和局部血流动力学紊乱的一个重要因素。
