Pharmacologic stimulation of the nicotinic anti-inflammatory pathway modulates gut and lung injury after hypoxia-reoxygenation injury.
Pharmacologic stimulation of the nicotinic anti-inflammatory pathway modulates gut and lung injury after hypoxia-reoxygenation injury.
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DOI：
10.1016/j.surg.2013.07.018
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发表时间：
2013-10
期刊：
影响因子：
3.8
通讯作者：
Samantha Tarras;L. Diebel;D. Liberati;Kevin R. Ginnebaugh
中科院分区：
文献类型：
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作者：
Samantha Tarras;L. Diebel;D. Liberati;Kevin R. Ginnebaugh
目的损伤前迷走神经刺激对实验性失血性休克（HS）后肠、肺损伤的保护作用。这可能通过胆碱能抗炎途径和α7烟碱乙酰胆碱受体（α 7 nAChR）发生。我们假设，在体外模型中，无论是尼古丁或选择性α 7 nAChR激动剂（AR-R17779）将调节肠和肺的肠道缺血-再灌注后缺氧insulation.MethodsConfluent HT 29肠上皮细胞与大肠杆菌共培养。将细胞培养物置于21%（对照）或5% O2（缺氧）中90分钟，然后再复氧（H/R）。用尼古丁或AR-R17779处理HT 29细胞，分别于缺氧前和缺氧后即刻测定细胞培养上清中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的含量。汇合的肺微血管上皮细胞（HMVEC）共培养与HT 29上清液和渗透性和细胞间粘附分子-1的表达determined.ResultsIn后H/R损伤治疗与受体激动剂，细胞因子水平在HT 29细胞降低到对照水平。在HMVEC实验中，在H/R损伤后的治疗中观察到保护作用。破坏HT 29肌动蛋白微丝被证明H/R损伤后，被废除由两个agonist.ConclusionPost-insult药理学刺激似乎模仿前HS迷走神经刺激在动物研究中看到的保护作用。
PurposePre-injury vagal nerve stimulation protects against gut and lung injury after experimental hemorrhagic shock (HS). This likely occurs via the cholinergic anti-inflammatory pathway and the α7 nicotinic acetylcholine receptor (α7nAChR). We hypothesized that, in an in vitro model, either nicotine or a selective α7nAChR agonist (AR-R17779) would modulate intestinal and pulmonary effects of gut ischemia-reperfusion after hypoxic insult.MethodsConfluent HT29 intestinal epithelial cells were co-cultured with Escherichia coli. Cell cultures were subjected to 21% (control) or 5% O2(hypoxia) for 90 minutes followed by reoxygenation (H/R). HT29 cells were treated with nicotine or AR-R17779 before or immediately after hypoxic insult. From the HT29 cell culture supernatants, tumor necrosis factor-α and interleukin-6 levels were quantitated. Confluent pulmonary microvascular epithelial cells (HMVEC) were co-cultured with HT29 supernatants and permeability and intercellular adhesion molecule-1 expression were determined.ResultsIn post H/R insult treatments with the receptor agonist, cytokine levels in HT29 cells were reduced to control levels. In HMVEC experiments, a protective effect was seen with treatment post H/R injury. Disruption of HT29 actin microfilaments was demonstrated after H/R insult and was abrogated by both agonists.ConclusionPost-insult pharmacologic stimulation seems to mimic the protective effects of pre-HS vagal nerve stimulation seen in animal studies.