COPD急性加重期呼气冷凝液中性粒细胞趋化性增加与气道免疫功能障碍的关系

摘要 目的：探讨COPD急性加重期（AECOPD）呼气冷凝液中性粒细胞趋化性增加与气道免疫功能障碍的关系。方法：2018年4月到2021年5月选择在本院诊治的COPD患者88例作为研究对象,包括AECOPD患者48例（急性组）与COPD缓解期患者40例（缓解组）,检测两组中性粒细胞氧化吞噬百分率、呼气冷凝液CCL18与CC16含量、外周血T淋巴细胞亚群水平,同时记录气道总粘性阻力、气道总阻抗、近端气道粘性阻力等指标并进行相关性分析。结果：急性组的中性粒细胞氧化吞噬百分率低于缓解组（P<0.05）。急性组的呼气冷凝液CCL18、CC16含量与气道总粘性阻力、气道总阻抗、近端气道粘性阻力高于缓解组（P<0.05）。急性组的CD4⁺T淋巴细胞比例低于缓解组,CD8⁺T淋巴细胞高于缓解组（P<0.05）。二分类Logistic回归分析结果显示：中性粒细胞氧化吞噬百分率、气道总阻抗、CD4⁺T淋巴细胞比例、呼气冷凝液CCL18为导致AECOPD发生的重要因素（P<0.05）。结论：AECOPD患者伴随有呼气冷凝液CCL18、CC16含量增加与中性粒细胞氧化吞噬百分率降低,还伴随有气道阻力增加与免疫功能降低,中性粒细胞氧化吞噬百分率、气道总阻抗、CD4⁺T淋巴细胞比例、呼气冷凝液CCL18为导致AECOPD发生的重要因素。     

Circadian and sleep-deprivation variations of monophosphorylated MAP-Kinase in hypothalamus and pons of rats

Behavior and physiological changes are under the influence of circadian and homeostatic variations. Temporal alignment regulates timing of neurobiological phenomena, such as protein phosphorylation. In the current report, we describe the circadian and sleep homeostatic phosphorylated mitogen-activated protein kinase (MAP-K) variations in hypothalamus and pons of rats across 24 h as well as after sleep deprivation. In the circadian study, MAP-K expression showed a building-up profile during the dark phase in hypothalamus, whereas an increase across the lights-on period was found in pons. On the other hand, that phosphorylation of MAP-K in hypothalamus and pons displayed a significant reduction after sleep rebound period. Data demonstrate that MAP-K phosphorylation undergoes circadian and sleep homeostatic variations in brain areas linked to sleep modulation.     

Morning caffeine ingestion increases cognitive function and short-term maximal performance in footballer players after partial sleep deprivation

The aim of the present study was to evaluate the effects of caffeine ingestion and partial sleep deprivation at the end of night on cognitive and physical performance. In randomised order, fourteen football players (age: 23.57 ± 1.98 years; body weight: 59.57 ± 4.29 kg; height: 174.35 ± 5.07 cm) completed four test sessions at 08:00 h: after placebo or 3 mg·kg^?1 of caffeine ingestion during a reference night, RN (bed time: from 22:30 h to 07:00 h) or a night of partial sleep deprivation, PSD (bed time: from 22:30 h to 03:00 h). During each test session, participants assessed vigilance and reaction times and performed a series of tests: cancelation test, squat jumps (SJ), and the 30-s Wingate test (for the measurement of peak power, PP, and mean power, PM). During RN, results showed that PP, PM, SJ, and vigilance increased after caffeine ingestion in comparison with placebo (p < 0.001). Moreover, both simple and choice reactions were significantly better after caffeine ingestion in comparison with placebo ingestion (p < 0.05 and p < 0.001, respectively). Results showed that reaction time, vigilance, and SJ were affected by PSD, even though PP, PM, and SJ were not affected, the following day at 08:00 h. During the PSD condition, PP, PM, SJ, and vigilance were significantly higher after caffeine ingestion in comparison with placebo ingestion (p < 0.001). However, both simple and choice reaction times were significantly poorer during PSD in comparison with RN (p < 0.05 and p < 0.001, respectively). Therefore, ingesting caffeine is an effective strategy to maintain physical and cognitive performances after PSD.     

Petchiether A attenuates obstructive nephropathy by suppressing TGF‐β/Smad3 and NF‐κB signalling

Obstructive nephropathy is the end result of a variety of diseases that block drainage from the kidney(s). Transforming growth factor‐β1 (TGF‐β1)/Smad3‐driven renal fibrosis is the common pathogenesis of obstructive nephropathy. In this study, we identified petchiether A (petA), a novel small‐molecule meroterpenoid from Ganoderma, as a potential inhibitor of TGF‐β1‐induced Smad3 phosphorylation. The obstructive nephropathy was induced by unilateral ureteral obstruction (UUO) in mice. Mice received an intraperitoneal injection of petA/vehicle before and after UUO or sham operation. An in vivo study revealed that petA protected against renal inflammation and fibrosis by reducing the infiltration of macrophages, inhibiting the expression of proinflammatory cytokines (interleukin‐1β and tumour necrosis factor‐α) and reducing extracellular matrix deposition (α‐smooth muscle actin, collagen I and fibronectin) in the obstructed kidney of UUO mice; these changes were associated with suppression of Smad3 and NF‐κB p65 phosphorylation. Petchiether A inhibited Smad3 phosphorylation in vitro and down‐regulated the expression of the fibrotic marker collagen I in TGF‐β1‐treated renal epithelial cells. Further, we found that petA dose‐dependently suppressed Smad3‐responsive promoter activity, indicating that petA inhibits gene expression downstream of the TGF‐β/Smad3 signalling pathway. In conclusion, our findings suggest that petA protects against renal inflammation and fibrosis by selectively inhibiting TGF‐β/Smad3 signalling.     

Molecular mechanism of tumour necrosis factor alpha regulates hypocretin (orexin) expression,sleep and behaviour

Hypocretin 1 and hypocretin 2 (orexin A and B) regulate sleep, wakefulness and emotion. Tumour necrosis factor alpha (TNF‐α) is an important neuroinflammation mediator. Here, we examined the effects of TNF‐α treatment on hypocretin expression in vivo and behaviour in mice. TNF‐α decreased hypocretin 1 and hypocretin 2 expression in a dose‐dependent manner in cultured hypothalamic neurons. TNF‐α decreased mRNA stability of prepro‐hypocretin, the single precursor of hypocretin 1 and hypocretin 2. Mice challenged with TNF‐α demonstrated decreased expression of prepro‐hypocretin, hypocretin 1 and hypocretin 2 in hypothalamus. In response to TNF‐α, prepro‐hypocretin mRNA decay was increased in hypothalamus. TNF‐α neutralizing antibody restored the expression of prepro‐hypocretin, hypocretin 1 and hypocretin 2 in vivo in TNF‐α challenged mice, supporting hypocretin system can be impaired by increased TNF‐α through decreasing hypocretin expression. Repeated TNF‐α challenge induced muscle activity during rapid eye movement sleep and sleep fragmentation, but decreased learning, cognition and memory in mice. TNF‐α neutralizing antibody blocked the effects of TNF‐α; in contrast, hypocretin receptor antagonist enhanced the effects of TNF‐α. The data support that TNF‐α is involved in the regulation of hypocretin expression, sleep and cognition. The findings shed some lights on the role of neuroinflammation in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease.     

阻塞性睡眠呼吸暂停低通气综合征血压变异性及运动心肺功能与病情的相关性分析

目的:探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)血压变异性及运动心肺功能与病情的相关性分析。方法:选取2017年2月～2018年11月期间我院收治的OSAHS患者119例为研究对象,根据每小时睡眠呼吸暂停次数(AHI)将患者分为轻度组(AHI:5～20次/h,n=45)、中度组(AHI:21～40次/h,n=39)、重度组(AHI:40次/h,n=35),检测所有研究对象的血压变异性及运动心肺功能,并作组间比较。采用Pearson积矩相关分析OSAHS患者血压变异性及运动心肺功能与病情的相关性。结果:OSAHS患者收缩压(SBP)昼、舒张压(DBP)夜以及中度组、重度组SBP夜均高于对照组(P0.05);重度组DBP夜以及中度组、重度组SBP昼、SBP夜高于轻度组(P0.05);重度组SBP夜、SBP昼、DBP夜高于中度组(P0.05);而各组DBP昼整体比较差异无统计学意义(P0.05)。OSAHS患者最大摄氧量占预计值百分比(VO2max%pred)、最大摄氧量峰值占预计值百分比(peak VO2%pred)、无氧阈值(AT)、摄氧量功率比值(VO2/WR)、呼吸储备(VEmax/MVV)均低于对照组,且随病情严重程度的增加而降低(P0.05),OSAHS患者二氧化碳通气当量(VE/VCO2)高于对照组,且随病情严重程度的增加而升高(P0.05)。Pearson积矩相关分析结果显示,OSAHS患者病情严重程度与SBP昼、SBP夜、DBP夜、VE/VCO2呈正相关(P0.05),与VO2max%pred、peakVO2%pred、AT、VEmax/MVV、VO2/WR呈负相关(P0.05),与DBP昼无相关性(P0.05)。结论:血压变异性及运动心肺功能指标可反映OSAHS患者病情严重程度,可考虑作为早期监测指标并参考指导治疗。     

丹参注射液联合莫西沙星治疗老年慢阻肺急性发作患者的疗效分析

目的:探讨丹参注射液联合莫西沙星治疗老年慢性阻塞性肺病急性加重患者的疗效及对血清可溶性髓样细胞触发受体-1(STREM-1)、白细胞介素-6(IL-6)、中性粒细胞CD64(CD64)及炎症因子水平的影响。方法:选择2015年5月到2017年5月我院接诊的老年慢性阻塞性肺病急性加重患者95例作为研究对象,根据随机数表法分为观察组(n=49)和对照组(n=46)。对照组使用莫西沙星治疗,观察组采用丹参注射液联合莫西沙星治疗。比较两组治疗后的疗效、治疗前后血清STREM-1、IL-6、CD64、炎症因子[肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)、降钙素原(PCT)]水平、肺功能的变化及不良反应的发生情况。结果:治疗后,观察组临床疗效总有效率为95.92%,显著高于对照组(76.09%,P0.05);观察组患者血清STREM-1、IL-6、CD64、TNF-α、CRP及PCT水平均明显低于对照组(P0.05);观察组FEV1、FVC、FEV1%预测值均明显高于对照组(P0.05);两组患者不良反应总发生率分别6.12%、13.04%,组间比较差异无统计学意义(P0.05)。结论:丹参注射液联合莫西沙星治疗老年慢性阻塞性肺病患者的临床效果显著优于单用莫西沙星治疗,可能与其有效改善患者血清STREM-1、IL-6、CD64水平及炎症因子水平有关。     

不同香烟烟雾暴露强度对大鼠骨骼肌线粒体功能的影响

目的:探讨不同烟熏暴露强度对大鼠外周骨骼肌线粒体功能的影响。方法:将SD大鼠随机分成4个组,分别接受正常空气或3个周期烟熏暴露(分别是4周、8周、12周)。采用western blot检测大鼠外周骨骼肌与线粒体生成有关的过氧化物酶体增殖物激活受体γ共激活因子1(PGC-1α)以及涉及氧化磷酸化的细胞色素c氧化酶(COX)4的蛋白表达,RT-PCR检测与线粒体氧化代谢有关的Sdhb、线粒体转录因子A(TFAM)的基因表达以及比色法检测琥珀酸脱氢酶(SDH)活性,电镜检测线粒体形态结构的改变。结果:香烟烟雾暴露能够下调大鼠伸趾长肌(EDL)PGC-1α和COX4的蛋白表达,PGC-1α的表达下调呈明显的暴露强度依赖性。香烟烟雾暴露能够诱发大鼠比目鱼肌Sdhb、TFAM基因水平的下调,降低大鼠比目鱼肌SDH活性并呈明显的暴露强度依赖性。电镜显示香烟烟雾暴露诱发伸趾长肌线粒体发生空泡样变性。结论:香烟烟雾暴露诱发大鼠骨骼肌线粒体功能障碍,但该作用与骨骼肌的纤维类型组成无明显相关性。     

头孢他啶联合氨茶碱治疗慢性阻塞性肺气肿的疗效及对血清IGF-1、α1-AT、PDGF-B水平的影响

目的:探讨头孢他啶联合氨茶碱治疗慢性阻塞性肺气肿(COPD)的临床疗效及对患者血清胰岛素样生长因子-1(IGF-1)、血清α1-抗胰蛋白酶(α1-AT)、血小板衍生生长因子-B(PDGF-B)水平的影响。方法:选择我院2015年4月至2018年4月收治的154例慢性阻塞性肺气肿作为研究对象,采用随机数字表法将其分为观察组与对照组。对照组采用头孢他啶治疗,观察组在对照组基础上加用氨茶碱联合治疗。对比两组患者的临床疗效、治疗前后血清IGF-1、α1-AT、PDGF-B水平的变化及不良反应的发生情况。结果:治疗后,观察组与对照组临床疗效总有效率分别为94.80%和71.43%,观察组显著高于对照组(P0.05);观察组血清IGF-1、PDGF-B水平均显著低于对照组[(110.67±13.58) vs.(143.17±15.74)ng/ml、(128.67±15.33) vs.(247.69±30.17)ng/L],而血清α1-AT水平明显高于对照组[(2.79±0.43) vs.(1.77±0.46)g/L](P0.05);观察组与对照组不良反应率分别为5.19%和50.64%,观察组明显低于对照组(P0.05)。结论:综上所述,头孢他啶联合氨茶碱治疗COPD的临床疗效和安全性均显著优于单用头孢他啶治疗,可能与其有效降低COPD患者血清PDGF-B、IGF-1,明显提高血清α1-AT水平有关。