腹部手术诱发大鼠胃麻痹及胃肌间神经丛中M1样巨噬细胞活化:中枢迷走神经激活的预防作用
Abdominal surgery induced gastric ileus and activation of M1-like macrophages in the gastric myenteric plexus: prevention by central vagal activation in rats.
作者信息
Yuan Pu-Qing, Taché Yvette
机构信息
CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Digestive Diseases Division, Department of Medicine and Brain Research Institute, University of California, Los Angeles, California; and
CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress and Resilience, Vatche and Tamar Manoukian Digestive Diseases Division, Department of Medicine and Brain Research Institute, University of California, Los Angeles, California; and.
出版信息
Am J Physiol Gastrointest Liver Physiol. 2017 Oct 1;313(4):G320-G329. doi: 10.1152/ajpgi.00121.2017. Epub 2017 Jul 6.
Inflammation plays a role in abdominal surgery (AS)-induced intestinal ileus that is alleviated by electrical vagal stimulation. Intracisternal injection of RX-77368, the stable thyrotropin-releasing hormone agonist, activates dorsal motor nucleus neurons and gastric vagal efferent discharges. We investigated the gastric inflammation induced by AS and the modulation by intracisternal RX-77368 in rats. RX-77368 (50 ng/rat) or saline was injected followed, 1 h later, by laparotomy and small intestinal/cecal manipulation. The sham group had anesthesia alone. After 6 h, gastric emptying (GE) and the inflammation in gastric corpus were determined. AS inhibited GE by 72% vs. control and doubled the number of M1-like macrophage immunoreactive for major histocompatibility complex class II (MHCII; M1 marker) but not for cluster of differentiation 206 (CD206; M2 marker) (MHCII/CD206) while there was no change in M2-like macrophages (MHCII/CD206). AS increased mRNA levels of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) by 1.7- and 1.5-fold, respectively, in the gastric submucosa plus muscle layers and the infiltration of neutrophils labeled by myeloperoxidase by 9.5-fold in the muscularis externa. RX-77368 inhibited AS-related gastric changes while not altering these parameters in the sham group. There was a significant negative correlation between GE and IL-1β ( = -0.46), TNF-α ( = -0.44), M1 macrophage ( = -0.82), and neutrophils ( = -0.91). The M2-like macrophages and IL-10 expression were unchanged by AS with intracisternal saline or RX-77368. These data indicate that AS activates gastric M1 macrophages and increases proinflammatory cytokines expression, which are prevented by central vagal activation and may contribute to the correlated dampening of postoperative gastric ileus. MHCII/CD206 (M1) and MHCII/CD206 (M2) constitute two distinct populations of macrophages that are in close apposition to the cholinergic neurons in the rat gastric myenteric plexus (MP). Abdominal surgery (6 h) activates M1 macrophage leading to inflammation in the gastric MP correlated with the delayed gastric emptying, which was abolished by central vagal stimulation via intracisternal injection of RX-77368. Vagal stimulation linked with the cephalic phase may have potential beneficial effects to curtail postoperative gastric ileus.
炎症在腹部手术(AS)诱导的肠梗阻中起作用,而电刺激迷走神经可缓解这种肠梗阻。脑池内注射稳定的促甲状腺激素释放激素激动剂RX - 77368可激活迷走神经背核神经元和胃迷走神经传出放电。我们研究了大鼠AS诱导的胃炎症以及脑池内注射RX - 77368对其的调节作用。注射RX - 77368(50 ng/只大鼠)或生理盐水,1小时后进行剖腹术并对小肠/盲肠进行操作。假手术组仅接受麻醉。6小时后,测定胃排空(GE)和胃体部的炎症情况。与对照组相比,AS使GE降低了72%,使主要组织相容性复合体II类(MHCII;M1标志物)免疫反应性的M1样巨噬细胞数量增加了一倍,但对分化簇206(CD206;M2标志物)(MHCII/CD206)免疫反应性的M2样巨噬细胞数量没有影响。AS使胃黏膜下层加肌层中白细胞介素 - 1β(IL - 1β)和肿瘤坏死因子α(TNF - α)的mRNA水平分别增加了1.7倍和1.5倍,使肌层中髓过氧化物酶标记的中性粒细胞浸润增加了9.5倍。RX - 77368抑制了与AS相关的胃部变化,而对假手术组的这些参数没有改变。GE与IL - 1β(r = -0.46)、TNF - α(r = -0.44)、M1巨噬细胞(r = -0.82)和中性粒细胞(r = -0.91)之间存在显著负相关。脑池内注射生理盐水或RX - 77368时,AS对M2样巨噬细胞和IL - 10表达没有影响。这些数据表明,AS激活胃M1巨噬细胞并增加促炎细胞因子表达,中枢迷走神经激活可预防这些变化,这可能有助于减轻术后胃麻痹。MHCII/CD206(M1)和MHCII/CD206(M2)构成了大鼠胃肌间神经丛(MP)中与胆碱能神经元紧密相邻的两个不同巨噬细胞群体。腹部手术(6小时)激活M1巨噬细胞,导致胃MP炎症,与胃排空延迟相关,通过脑池内注射RX - 77368进行中枢迷走神经刺激可消除这种延迟。与头期相关的迷走神经刺激可能对减轻术后胃麻痹具有潜在的有益作用。