Time-dependent alteration in the chemoreflex post-acute lung injury.
Time-dependent alteration in the chemoreflex post-acute lung injury.
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DOI：
10.3389/fphys.2022.1009607
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发表时间：
2022
影响因子：
4
通讯作者：
Wang, Han-Jun
中科院分区：
文献类型：
--
作者：
Kamra, Kajal;Karpuk, Nikolay;Adam, Ryan;Zucker, Irving H.;Schultz, Harold D.;Wang, Han-Jun
关键词：
急性肺损伤（ALI）会引发炎症，破坏正常的肺泡 - 毛细血管内皮屏障，进而损害气体交换，导致低氧血症，低氧血症又会反射性地使呼吸加快。目前，ALI期间呼吸功能障碍背后的神经机制尚未完全明晰。本研究旨在探究化学反射在ALI急性期（早期）和恢复期（晚期）介导异常通气中的作用。我们假设，ALI后呼吸频率（fR）的增加是由敏感化的化学反射介导的。通过向雄性Sprague - Dawley大鼠气管内单次注射博来霉素（Bleo：低剂量 = 1.25毫克/千克或高剂量 = 2.5毫克/千克）（第1天）诱导ALI，并从第0周（W0）至第4周（W4）每周使用全身体积描记法（WBP）测量呼吸变量——fR、潮气量（Vt）和分钟通气量（VE），以观察其对10% 低氧（10% O₂，0% CO₂）和5% 高碳酸血症/21% 常氧（21% O₂，5% CO₂）的反应。我们的数据表明，在低剂量博来霉素（中度ALI）组中，ALI后第1周（W1），化学反射对低氧/高碳酸血症气体刺激敏感化（ΔfR = 93 ± 31次/分钟，p < 0.0001）；而在高剂量博来霉素（重度ALI）组中，ALI后W1化学反射减弱（ΔfR = - 0.97 ± 42次/分钟，p < 0.0001）。在ALI恢复阶段，即W3 - W4，低剂量组和高剂量组对低氧和常氧 - 高碳酸血症均表现出敏感化的化学反射。随后我们假设，高剂量博来霉素组ALI后W1化学反射减弱可能是由于化学感受器近乎最大程度的紧张性激活，即所谓的“天花板效应”。为验证这一可能性，给博来霉素处理的大鼠吸入90% 高氧（90% O₂，0% CO₂）以抑制化学反射。我们的结果显示fR无变化，这表明ALI后W1时，对低氧不存在紧张性化学反射激活。这些数据表明，在中度（低剂量博来霉素）和重度（高剂量博来霉素）ALI急性期，化学反射活动分别呈轻度敏感化和减弱趋势，而在恢复期则显著敏感化。未来需要进一步研究以探究ALI后化学反射敏感性随时间变化背后的分子/细胞机制。
Acute lung injury (ALI) induces inflammation that disrupts the normal alveolar-capillary endothelial barrier which impairs gas exchange to induce hypoxemia that reflexively increases respiration. The neural mechanisms underlying the respiratory dysfunction during ALI are not fully understood. The purpose of this study was to investigate the role of the chemoreflex in mediating abnormal ventilation during acute (early) and recovery (late) stages of ALI. We hypothesized that the increase in respiratory rate (fR) during post-ALI is mediated by a sensitized chemoreflex. ALI was induced in male Sprague-Dawley rats using a single intra-tracheal injection of bleomycin (Bleo: low-dose = 1.25 mg/Kg or high-dose = 2.5 mg/Kg) (day 1) and respiratory variables- fR, Vt (Tidal Volume), and VE (Minute Ventilation) in response to 10% hypoxia (10% O2, 0% CO2) and 5% hypercapnia/21% normoxia (21% O2, 5% CO2) were measured weekly from W0-W4 using whole-body plethysmography (WBP). Our data indicate sensitization (∆fR = 93 ± 31 bpm, p < 0.0001) of the chemoreflex at W1 post-ALI in response to hypoxic/hypercapnic gas challenge in the low-dose bleo (moderate ALI) group and a blunted chemoreflex (∆fR = −0.97 ± 42 bpm, p < 0.0001) at W1 post-ALI in the high-dose bleo (severe ALI) group. During recovery from ALI, at W3-W4, both low-dose and high-dose groups exhibited a sensitized chemoreflex in response to hypoxia and normoxic-hypercapnia. We then hypothesized that the blunted chemoreflex at W1 post-ALI in the high-dose bleo group could be due to near maximal tonic activation of chemoreceptors, called the “ceiling effect”. To test this possibility, 90% hyperoxia (90% O2, 0% CO2) was given to bleo treated rats to inhibit the chemoreflex. Our results showed no changes in fR, suggesting absence of the tonic chemoreflex activation in response to hypoxia at W1 post-ALI. These data suggest that during the acute stage of moderate (low-dose bleo) and severe (high-dose bleo) ALI, chemoreflex activity trends to be slightly sensitized and blunted, respectively while it becomes significantly sensitized during the recovery stage. Future studies are required to examine the molecular/cellular mechanisms underlying the time-course changes in chemoreflex sensitivity post-ALI.
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DOI：
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发表时间：
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期刊：
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影响因子：
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