Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
Department of Pathology, University of Leuven, Leuven, Belgium.
Gut. 2016 Jan;65(1):73-81. doi: 10.1136/gutjnl-2014-308154. Epub 2014 Nov 19.
Impaired gastric accommodation is reported in patients with functional dyspepsia (FD). Previous findings in postinfectious patients with FD suggest that low-grade inflammation and dysfunction of nitrergic nerves play a role in impaired accommodation. To date, spontaneous animal models to study the relationship between these changes are lacking. We hypothesise that the normoglycaemic BioBreeding diabetes-prone (BB-DP) rat provides an animal model of inflammation-induced impaired gastric motor function.
Control diabetes-resistant biobreeding, normoglycaemic and hyperglycaemic BB-DP rats were sacrificed at the age of 30, 70 and 220 days and gastric fundus tissue was harvested to study nitrergic motor control, inflammation and expression of neuronal isoform of nitric oxide synthase (nNOS) and inducible isoform of nitric oxide synthase (iNOS). Nutrient-induced changes in intragastric pressure (IGP) were measured in normoglycaemic BB-DP rats to study accommodation.
No differences in nitrergic function and inflammation were observed between BB-DP and control rats at 30 days. The nitrergic component of the fundic muscle relaxation was reduced in BB-DP rats of 70 and 220 days. This was accompanied by a significant loss of nNOS proteins. IGP significantly increased during nutrient infusion in BB-DP rats of 220 days, indicating impaired accommodation. Infiltration of polymorphonuclear cells, increased myeloperoxidase activity and increased expression of iNOS was observed in the fundic mucosa and muscularis propria of 70-day-old and 220-day-old BB-DP rats.
BB-DP rats of 220 days display altered fundic motor control and impaired accommodation, which is least partially explained by loss of nitrergic function. This may be related to inflammatory changes in the neuromuscular layer, suggesting that normoglycaemic BB-DP rats provide a spontaneous model for inflammation-induced impaired gastric accommodation.
功能性消化不良（FD）患者的胃容纳功能受损。先前在 FD 的感染后患者中的发现表明，低度炎症和氮能神经功能障碍在胃容纳功能受损中发挥作用。迄今为止，缺乏研究这些变化之间关系的自发性动物模型。我们假设正常血糖的 BioBreeding 糖尿病易感（BB-DP）大鼠提供了一种炎症诱导的胃运动功能障碍的动物模型。
在 30、70 和 220 天龄时，处死对照糖尿病抗性生物繁殖、正常血糖和高血糖 BB-DP 大鼠，并采集胃底组织以研究氮能运动控制、炎症以及神经元型一氧化氮合酶（nNOS）和诱导型一氧化氮合酶（iNOS）的表达。在正常血糖的 BB-DP 大鼠中测量营养引起的胃内压（IGP）变化，以研究容纳功能。
在 30 天时，BB-DP 大鼠与对照大鼠之间的氮能功能和炎症无差异。70 天和 220 天的 BB-DP 大鼠胃底肌肉松弛的氮能成分减少。这伴随着 nNOS 蛋白的显著丢失。在 220 天的 BB-DP 大鼠中，营养输注时 IGP 显著增加，表明容纳功能受损。在 70 天和 220 天的 BB-DP 大鼠的胃底黏膜和肌层中观察到多形核细胞浸润、髓过氧化物酶活性增加和 iNOS 表达增加。
220 天龄的 BB-DP 大鼠表现出胃底运动控制改变和容纳功能受损，这至少部分是由于氮能功能丧失所致。这可能与神经肌肉层的炎症变化有关，表明正常血糖的 BB-DP 大鼠提供了一种自发性模型，用于研究炎症诱导的胃容纳功能障碍。
