迷走神经在STM感染大鼠维持免疫平衡及将免疫信息从肠道传递至大脑中的作用证据。
Evidences for vagus nerve in maintenance of immune balance and transmission of immune information from gut to brain in STM-infected rats.
作者信息
Wang Xi, Wang Bai-Ren, Zhang Xi-Jing, Xu Zhen, Ding Yu-Qiang, Ju Gong
机构信息
Institute of Neurosciences, The Fourth Military Medical University, Xi'an, Shaanxi Province, China.
出版信息
World J Gastroenterol. 2002 Jun;8(3):540-5. doi: 10.3748/wjg.v8.i3.540.
AIM
To determine whether Salmonella Typhimurium (STM)in gastrointestinal tract can induce the functional activation of brain, whether the vagus nerve involves in signaling immune information from gastrointestinal tract to brain and how it influences the immune function under natural infection condition.
METHODS
Animal model of gastrointestinal tract infection in the rat was established by an intubation of Salmonella Typhimurium (STM) into stomach to mimic the condition of natural bacteria infection. Subdiagphragmatic vagotomy was performed in some of the animals 28 days before infection. The changes of Fos expression visualized with immunohistochemistry technique in hypothalamic paraventricular nucleus (PVN) and superaoptic nucleus (SON) were counted. Meanwhile, the percentage and the Mean Intensities of Fluorescent (MIFs) of CD4+ and CD8+ T cells in peripheral blood were measured by using flow cytometry (FCM), and the pathological changes in ileum and mesenteric lymph node were observed in HE stained sections.
RESULTS
In bacteria-stimulated groups, inflammatory pathological changes were seen in ileum and mesenteric lymph node. The percentages of CD4+ T cells in peripheral blood were decreased from 42%+/-4.5% to 34%+/-4.9% (P<0.05) and MIFs of CD8+ T cells were also decreased from 2.9+/-0.39 to 2.1+/-0.36 (P<0.05) with STM stimulation. All of them proved that our STM-infection model was reliable. Fos immunoreactive (Fos-ir) cells in PVN and SON increased significantly with STM stimulation, from 189+/-41 to 467+/-62 (P<0.05) and from 64+/-21 to 282+/-47 (P<0.05) individually, which suggested that STM in gastrointestinal tract induced the functional activation of brain. Subdiagphragmatic vagotomy attenuated Fos expression in PVN and SON induced by STM, from 467+/-62 to 226+/-45 (P<0.05) and from 282+/-47 to 71+/-19 (P<0.05) individually, and restored the decreased percentages of CD4+ T cells induced by STM from 34%+/-4.9% to original level 44%+/-6.0% (P<0.05). In addition, subdiagphragmatic vagotomy itself also decreased the percentages of CD8+ T cells (from 28%+/-3.0% to 21%+/-5.9%, P<0.05) and MIFs of CD4+ (from 6.6+/-0.6 to 4.9+/-1.0, P<0.05) and CD8+ T cells (from 2.9+/-0.39 to 1.4+/-0.34, P<0.05). Both of them manifested the important role of vagus nerve in transmitting immune information from gut to brain and maintaining the immune balance of the organism.
CONCLUSION
Vagus nerve does involve in transmitting abdominal immune information into the brain in STM infection condition and play an important role in maintenance of the immune balance of the organism.
目的
确定胃肠道中的鼠伤寒沙门氏菌（STM）是否能诱导大脑功能激活，迷走神经是否参与从胃肠道向大脑传递免疫信息以及在自然感染条件下它如何影响免疫功能。
方法
通过将鼠伤寒沙门氏菌（STM）经胃插管建立大鼠胃肠道感染动物模型，以模拟自然细菌感染情况。在感染前28天对部分动物进行膈下迷走神经切断术。采用免疫组织化学技术对下丘脑室旁核（PVN）和视上核（SON）中可视化的Fos表达变化进行计数。同时，使用流式细胞术（FCM）检测外周血中CD4⁺和CD8⁺T细胞的百分比及荧光平均强度（MIFs），并在苏木精-伊红（HE）染色切片中观察回肠和肠系膜淋巴结的病理变化。
结果
在细菌刺激组中，回肠和肠系膜淋巴结出现炎症病理变化。经STM刺激后，外周血中CD4⁺T细胞百分比从42%±4.5%降至34%±4.9%（P<0.05），CD8⁺T细胞的MIFs也从2.9±0.39降至2.1±0.36（P<0.05）。所有这些都证明我们的STM感染模型是可靠的。经STM刺激后，PVN和SON中的Fos免疫反应性（Fos-ir）细胞显著增加，分别从189±41增至467±62（P<0.05）和从64±21增至282±47（P<0.05），这表明胃肠道中的STM诱导了大脑功能激活。膈下迷走神经切断术减弱了STM诱导的PVN和SON中的Fos表达，分别从467±62降至226±45（P<0.05）和从282±47降至71±19（P<0.05），并将STM诱导降低的CD4⁺T细胞百分比从34%±4.9%恢复到原始水平44%±6.0%（P<0.05）。此外，膈下迷走神经切断术本身也降低了CD8⁺T细胞百分比（从28%±3.0%降至21%±5.9%，P<0.05）以及CD4⁺（从6.6±0.6降至4.9±1.0，P<0.05）和CD8⁺T细胞的MIFs（从2.9±0.39降至1.4±0.34，P<0.05）。这两者都表明迷走神经在从肠道向大脑传递免疫信息以及维持机体免疫平衡中起重要作用。
结论
在STM感染条件下，迷走神经确实参与将腹部免疫信息传递至大脑，并在维持机体免疫平衡中起重要作用。
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