BACKGROUND:The aim of this study was to investigate whether a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) inhibitor, apocynin, reduces reactive oxygen species (ROS) production, suppresses the nuclear factor κB (NF-κB) pathway, attenuates lung injury, and improves survival in rat hemorrhagic shock (HS) model.
METHODS:Blood was drawn from male Sprague-Dawley rats (290-340 g) to maintain a mean arterial pressure of 20-25 mm Hg for 40 minutes. The rats were resuscitated with the drawn blood, and a vehicle (HS), a low dose of apocynin (20 mg/kg, LD-Apo), or a high dose of apocynin (40 mg/kg, HD-Apo) was administered intraperitoneally. The survival of the rats was observed for 72 hours. Then, a separated set of rats was euthanized at 6 hours post-HS induction. We measured gp91-phox (Nox2) expression, Nox activity, cytoplasmic phosphorylated inhibitor κB-α (p-IκB-α) expression, NF-κB p65 DNA-binding activity, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) gene expressions, malondialdehyde (MDA) level, myeloperoxidase (MPO) activity, and histological damage in the lung tissues.
RESULTS:The survival rates of the sham, HS, HS + LD-Apo, and HS + HD-Apo groups were 100% (5/5), 30% (3/10), 40% (4/10), and 70% (7/10), respectively. A high dose of apocynin decreased gp91-phox expression, Nox activity, and MDA level in the lung tissues during HS and resuscitation. It also decreased p-IκB-α expression, NF-κB p65 DNA-binding activity, TNF-α and IL-6 gene expressions, and MPO activity in the lung tissues and attenuated histological lung injuries. However, a low dose of apocynin failed to show these benefits.
CONCLUSIONS:The administration of a high dose of apocynin inhibited Nox2 expression and Nox activity, reduced lipid peroxidation, suppressed the NF-κB pathway and subsequent pro-inflammatory cytokines transcription in the lung tissues, and attenuated lung injury during HS and resuscitation in rats.
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【Apocynin suppressed the nuclear factor-κB pathway and attenuated lung injury in a rat hemorrhagic shock model.].
【在大鼠失血性休克模型中，Apocynin抑制了核因子-κB通路并减轻了肺损伤。】
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DOI：10.1097/TA.0000000000001337文章类型：杂志文章
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背景：本研究的目的是研究烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（Nox）抑制剂，载脂蛋白Ayn，减少活性氧（ROS）的产生，抑制核因子κB（NF-κB）途径，减弱肺功能损伤，并提高大鼠失血性休克（HS）模型的存活率。
方法：从雄性Sprague-Dawley大鼠（290-340 g）抽取血液，以维持20-25 mm Hg的平均动脉压40分钟。用抽血使大鼠复苏，并给予媒介物（HS），低剂量的Apocynin（20 mg / kg，LD-Apo）或高剂量的Apocynin（40 mg / kg，HD-Apo）腹膜内。观察大鼠的存活72小时。然后，在HS诱导后6小时对一组分离的大鼠实施安乐死。我们测量了gp91-phox（Nox2）表达，Nox活性，胞质磷酸化抑制剂κB-α（p-IκB-α）表达，NF-κBp65 DNA结合活性，肿瘤坏死因子-α（TNF-α）和白介素-肺组织中的6（IL-6）基因表达，丙二醛（MDA）水平，髓过氧化物酶（MPO）活性和组织学损伤。
结果：假，HS，HS LD-Apo和HS HD-Apo组的生存率分别为100％（5/5），30％（3/10），40％（4/10）和70％ （7/10）。高剂量的载脂蛋白在HS和复苏过程中会降低肺组织中的gp91-phox表达，Nox活性和MDA水平。它还降低了肺组织中的p-IκB-α表达，NF-κBp65 DNA结合活性，TNF-α和IL-6基因表达以及MPO活性，减轻了肺组织学损伤。但是，低剂量的Apocynin未能显示出这些益处。
结论：高剂量的阿扑西宁可抑制Nox2的表达和Nox活性，减少脂质过氧化，抑制NF-κB通路，进而抑制肺组织中促炎性细胞因子的转录，并减轻大鼠HS和复苏中的肺损伤。
方法：从雄性Sprague-Dawley大鼠（290-340 g）抽取血液，以维持20-25 mm Hg的平均动脉压40分钟。用抽血使大鼠复苏，并给予媒介物（HS），低剂量的Apocynin（20 mg / kg，LD-Apo）或高剂量的Apocynin（40 mg / kg，HD-Apo）腹膜内。观察大鼠的存活72小时。然后，在HS诱导后6小时对一组分离的大鼠实施安乐死。我们测量了gp91-phox（Nox2）表达，Nox活性，胞质磷酸化抑制剂κB-α（p-IκB-α）表达，NF-κBp65 DNA结合活性，肿瘤坏死因子-α（TNF-α）和白介素-肺组织中的6（IL-6）基因表达，丙二醛（MDA）水平，髓过氧化物酶（MPO）活性和组织学损伤。
结果：假，HS，HS LD-Apo和HS HD-Apo组的生存率分别为100％（5/5），30％（3/10），40％（4/10）和70％ （7/10）。高剂量的载脂蛋白在HS和复苏过程中会降低肺组织中的gp91-phox表达，Nox活性和MDA水平。它还降低了肺组织中的p-IκB-α表达，NF-κBp65 DNA结合活性，TNF-α和IL-6基因表达以及MPO活性，减轻了肺组织学损伤。但是，低剂量的Apocynin未能显示出这些益处。
结论：高剂量的阿扑西宁可抑制Nox2的表达和Nox活性，减少脂质过氧化，抑制NF-κB通路，进而抑制肺组织中促炎性细胞因子的转录，并减轻大鼠HS和复苏中的肺损伤。
