Jardí Ferran, Fernández-Blanco Joan A, Martínez Vicente, Vergara Patri
Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona , Barcelona , Spain.
Scand J Gastroenterol. 2014 Nov;49(11):1296-303. doi: 10.3109/00365521.2014.958524. Epub 2014 Sep 26.
Intestinal infections are suggested as a risk factor for the development of irritable bowel syndrome (IBS)-like visceral hypersensitivity. The mechanisms implicated might involve long-term changes in visceral afferents, with implication of nerve growth factor (NGF). We explored plastic changes in dorsal root ganglia (DRGs) receiving innervation from the gut and the potential implication of NGF in a rat model of IBS-like post-infectious gut dysfunction.
Rats were infected with Trichinella spiralis larvae. Thirty days post-infection, inflammatory markers, including interleukins (ILs) and mucosal mast cell infiltration (rat mast cell protease II [RMCPII]), and NGF and TrkA expression was determined in the jejunum and colon (RT-qPCR). In the same animals, morphometry (neuronal body size) and NGF content (immunofluorescence) were assessed in thoracolumbar DRG neurons.
In infected animals, a low-grade inflammatory-like response, characterized by up-regulated levels of RMCPII and IL-6, was observed in the jejunum and colon. TrkA expression was increased in the jejunum, whereas the colon showed a slight reduction. NGF levels remained unaltered regardless the gut region. Overall, the mean cross-sectional area of DRG neurons was increased in T. spiralis-infected animals, with a reduction in both TrkA and NGF staining.
Results suggest that during T. spiralis infection in rats, there is a remodeling of sensory afferents that might imply a NGF-mediated mechanism. Plastic changes in sensory afferents might mediate the long-lasting functional alterations that characterize this model of IBS. Similar mechanisms might be operating in patients with post-infectious-IBS.
肠道感染被认为是肠易激综合征（IBS）样内脏超敏反应发生的一个危险因素。其潜在机制可能涉及内脏传入神经的长期变化，并与神经生长因子（NGF）有关。我们在一个IBS样感染后肠道功能障碍的大鼠模型中，探究了接受来自肠道神经支配的背根神经节（DRG）的可塑性变化以及NGF的潜在作用。
大鼠感染旋毛虫幼虫。感染后30天，通过实时定量聚合酶链反应（RT-qPCR）测定空肠和结肠中的炎症标志物，包括白细胞介素（ILs）和黏膜肥大细胞浸润（大鼠肥大细胞蛋白酶II [RMCPII]），以及NGF和TrkA的表达。在同一批动物中，对胸腰段DRG神经元进行形态计量学分析（神经元胞体大小）和NGF含量评估（免疫荧光法）。
在感染动物中，空肠和结肠中观察到一种以RMCPII和IL-6水平上调为特征的轻度炎症样反应。空肠中TrkA表达增加，而结肠中略有降低。无论肠道区域如何，NGF水平均保持不变。总体而言，旋毛虫感染动物的DRG神经元平均横截面积增加，同时TrkA和NGF染色减少。
结果表明，在大鼠感染旋毛虫期间，感觉传入神经存在重塑，这可能意味着一种由NGF介导的机制。感觉传入神经的可塑性变化可能介导了该IBS模型所特有的长期功能改变。类似的机制可能在感染后IBS患者中起作用。
