Heat and Hypoxic Acclimation Increase Monocyte Heat Shock Protein 72 but Do Not Attenuate Inflammation following Hypoxic Exercise.

Heat and Hypoxic Acclimation Increase Monocyte Heat Shock Protein 72 but Do Not Attenuate Inflammation following Hypoxic Exercise.
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DOI:
10.3389/fphys.2017.00811
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发表时间:
2017
影响因子:
4
通讯作者:
Thake CD
Thake CD
中科院分区:
医学2区
文献类型:
--
作者:
Lee BJ;Thake CD

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热或缺氧应激的适应激活热休克反应和细胞保护性热休克蛋白(HSP)的积累。通过抑制NF-κB通路,HSP 72可以保护上皮功能并减轻全身炎症。本研究的目的是确定适应过程中mHSP 72积累的时间过程,并评估低氧运动后肠屏障损伤和全身炎症。三组在对照(n = 7; 18°C,35%RH)、低氧(n = 7; FiO 2 = 0.14,18° C,35%RH)或热(n = 7; 40°C,25%RH)条件下完成10 × 60分钟的适应期(50%常氧VO 2峰值)。在静息和循环常氧负荷试验后测定肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)、白细胞介素10(IL-10)和肠脂肪酸结合蛋白(I-FABP)(NST;适应前约2周),适应前低氧应激试验(HST 1; FiO 2 = 0.14,均为50%常氧VO 2峰值;驯化前约1周)和驯化后HST(48 h; HST 2)。分别于训练第1、3、5、6、10天,于运动前、运动后测定单核细胞HSP 72(mHSP 72)。基础mHSP 72的积累从热适应的第5天开始明显(p < 0.05),并且在第6天(p < 0.01)和第10天(p < 0.01)进一步增加。与此相反,基础mHSP 72在低氧习服的最后一天升高(p < 0.05)。NST后,血浆TNF-α(-0.11 ± 0.27 ng.mL−1)、IL-6(+0.62 ± 0.67 ng.mL−1)、IL-10(+1.09 ± 9.06 ng.mL−1)和I-FABP(+37.6 ± 112.8 pg.mL−1)的变化极小。HST 1后,IL-6(+3.87 ± 2.56 ng.mL-1)、IL-10(+26.15 ± 26.06 ng.mL-1)和I-FABP(+183.7 ± 182.1 pg.mL-1)升高(p < 0.01),而TNF-α无变化(+0.08 ± 1.27; p > 0.05)。HST 2后观察到类似趋势,IL-6(+3.09 ± 1.30 ng.mL−1)、IL-10(+23.22 ± 21.67 ng.mL−1)和I-FABP(+145.9 ±123.2 pg.mL−1)较静息时增加。热习服诱导mHSP 72积累的时间早,并在更大的幅度相比,匹配的工作低氧习服,但无论是习服制度衰减全身细胞因子反应或肠道损伤后急性运动低氧。
Acclimation to heat or hypoxic stress activates the heat shock response and accumulation of cytoprotective heat shock proteins (HSPs). By inhibiting the NF-κB pathway HSP72 can preserve epithelial function and reduce systemic inflammation. The aim of this study was to determine the time course of mHSP72 accumulation during acclimation, and to assess intestinal barrier damage and systemic inflammation following hypoxic exercise. Three groups completed 10 × 60-min acclimation sessions (50% normoxic VO2peak) in control (n = 7; 18°C, 35% RH), hypoxic (n = 7; FiO2 = 0.14, 18°C, 35% RH), or hot (n = 7; 40°C, 25% RH) conditions. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), and intestinal fatty acid binding protein (I-FABP) were determined at rest and following a cycling normoxic stress test (NST; ~2 weeks before acclimation), pre-acclimation hypoxic stress test (HST1; FiO2 = 0.14, both at 50% normoxic VO2peak; ~1 week before acclimation) and post-acclimation HST (48 h; HST2). Monocyte HSP72 (mHSP72) was determined before and after exercise on day 1, 3, 5, 6, and 10 of acclimation. Accumulation of basal mHSP72 was evident from day 5 (p < 0.05) of heat acclimation and increased further on day 6 (p < 0.01), and day 10 (p < 0.01). In contrast, basal mHSP72 was elevated on the final day of hypoxic acclimation (p < 0.05). Following the NST, plasma TNF-α (–0.11 ± 0.27 ng.mL−1), IL-6 (+0.62 ± 0.67 ng.mL−1) IL-10 (+1.09 ± 9.06 ng.mL−1) and I-FABP (+37.6 ± 112.8 pg.mL−1) exhibited minimal change. After HST1, IL-6 (+3.87 ± 2.56 ng.mL−1), IL-10 (+26.15 ± 26.06 ng.mL−1) and I-FABP (+183.7 ± 182.1 pg.mL−1) were elevated (p < 0.01), whereas TNF-α was unaltered (+0.08 ± 1.27; p > 0.05). A similar trend was observed after HST2, with IL-6 (+3.09 ± 1.30 ng.mL−1), IL-10 (+23.22 ± 21.67 ng.mL−1) and I-FABP (+145.9 ±123.2 pg.mL−1) increased from rest. Heat acclimation induces mHSP72 accumulation earlier and at a greater magnitude compared to matched work hypoxic acclimation, however neither acclimation regime attenuated the systemic cytokine response or intestinal damage following acute exercise in hypoxia.
人类肠道缺血再灌注的快速逆转通过脱落受伤的肠上皮细胞和再上皮化引起的损害。
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