Liu Lian-Sheng, Winston John H, Shenoy Mohan M, Song Geng-Qing, Chen Jiande D Z, Pasricha Pankaj Jay
Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California 94305-5187, USA.
Gastroenterology. 2008 Jun;134(7):2070-9. doi: 10.1053/j.gastro.2008.02.093. Epub 2008 Mar 8.
BACKGROUND & AIMS: Although several pathophysiologic abnormalities have been noted in functional dyspepsia (FD), their pathogenesis is poorly understood. We hypothesized that chronic gastric hypersensitivity and gastric motor dysfunction seen in FD patients can be modeled in rats by transient gastric irritation during the neonatal period, a time of known neuronal vulnerability to long-term plasticity.
Ten-day-old male rats received 0.2 mL 0.1% iodoacetamide (IA) in 2% sucrose daily by oral gavages for 6 days; controls received 2% sucrose. Rats in both groups were then followed to adulthood (8-10 weeks) at which point behavioral, visceromotor, and great splanchnic nerve responses to graded gastric balloon distention (GD; 20-80 mm Hg) and gastric motor function were tested.
IA-treated rats exhibited hypersensitivity to GD in a dose-dependent manner, as compared with the control group. The threshold of afferent nerve activation was lower and nerve responses to GD were significantly increased in IA-treated rats. Although IA-treated rats ingested food at a lower rate, gastric emptying was not significantly different between IA and control groups. However, gastric accommodation was significantly reduced in the IA group. No significant gastric pathology was seen in hypersensitive adult rats compared with controls.
These studies demonstrate that gastric irritation in the neonatal period can result in chronic gastric hypersensitivity and gastric motor dysfunction in adults even in the absence of significant detectable gastric pathology. Our results offer insight into the pathogenesis of chronic functional dyspepsia and provide a potential model for further study to this important clinical problem.
尽管在功能性消化不良（FD）中已发现多种病理生理异常，但其发病机制仍知之甚少。我们推测，FD患者中所见的慢性胃超敏反应和胃运动功能障碍可通过新生期短暂的胃刺激在大鼠中建模，新生期是已知神经元易受长期可塑性影响的时期。
10日龄雄性大鼠每天经口灌胃给予0.2 mL含0.1%碘乙酰胺（IA）的2%蔗糖溶液，持续6天；对照组给予2%蔗糖溶液。然后将两组大鼠饲养至成年（8 - 10周），此时测试其对分级胃气球扩张（GD；20 - 80 mmHg）的行为、内脏运动和内脏大神经反应以及胃运动功能。
与对照组相比，IA处理的大鼠对GD表现出剂量依赖性超敏反应。IA处理的大鼠传入神经激活阈值较低，对GD的神经反应显著增加。尽管IA处理的大鼠进食速度较低，但IA组和对照组之间的胃排空无显著差异。然而，IA组的胃容受性显著降低。与对照组相比，超敏成年大鼠未见明显的胃部病理改变。
这些研究表明，即使在没有明显可检测到的胃部病理改变的情况下，新生期的胃刺激也可导致成年大鼠出现慢性胃超敏反应和胃运动功能障碍。我们的结果为慢性功能性消化不良的发病机制提供了见解，并为进一步研究这一重要临床问题提供了潜在模型。
