背景:COPD是一个主要的全球健康问题,常伴有心血管疾病。大量证据表明,血小板的激活会增加心血管风险,炎症又加剧了这种情况。由于活性氧被认为是血小板代谢和功能的重要因素,本研究的目的是对慢性烟雾暴露的COPD样肺部病变动物的血小板线粒体功能进行复杂评估.
方法:八周大,雄性DunkinHartley豚鼠(研究组)暴露于来自商业未过滤香烟的香烟烟雾(0.9mg/cig尼古丁含量)或没有香烟烟雾的空气(对照组),使用CandelaConstructions®曝光系统。动物每天暴露4小时,一周五天,2×70毫升喷烟/分钟,直到观察到呼吸困难的迹象。动物们流血了,分离的血小板用于监测血小板呼吸。通过高分辨率呼吸测量法连续记录耗氧量,在体外监测血小板的线粒体呼吸参数。
结果:在暴露于烟雾的动物中,在LEAK状态下(根据血小板数量进行了调整)观察到呼吸趋势升高:6.75(5.09)vs2.53(1.28)(pmolO2/[s·1108血小板]);自举增强的P1α=0.04。研究组还显示出ET状态下的呼吸降低(蛋白质含量归一化):12.31(4.84)对16.48(1.72)(pmolO2/[s·mg蛋白质]);自举增强的P1α=0.049。
结论:我们的结果表明,慢性烟雾暴露动物的血小板中质子和电子泄漏增加,电子转移系统容量降低。这些观察结果还可能表明血小板在COPD及其合并症的病理生物学中起重要作用,并且可能作为可能的治疗靶向的背景。然而,这些初步结果应在基于更大样本的研究中进一步验证.
BACKGROUND: COPD represents a major global health issue, which is often accompanied by cardiovascular diseases. A considerable body of evidence suggests that cardiovascular risk is elevated by the activation of blood platelets, which in turn is exacerbated by inflammation. As reactive oxygen species are believed to be an important factor in platelet metabolism and functioning, the aim of our
study was to perform a complex assessment of mitochondrial function in platelets in chronic smoke exposed animals with COPD-like lung lesions.
METHODS: Eight-week-old, male Dunkin Hartley guinea pigs (the
study group) were exposed to the cigarette smoke from commercial unfiltered cigarettes (0.9 mg/cig of nicotine content) or to the air without cigarette smoke (control group), using the Candela Constructions® exposure system. The animals were exposed for 4 hours daily, 5 days a week, with 2×70 mL puff/minute, until signs of dyspnea were observed. The animals were bled, and isolated platelets were used to monitor blood platelet respiration. The mitochondrial respiratory parameters of the platelets were monitored in vitro based on continuous recording of oxygen consumption by high-resolution respirometry.
RESULTS: An elevated respiration trend was observed in the LEAK-state (adjusted for number of platelets) in the smoke-exposed animals: 6.75 (5.09) vs 2.53 (1.28) (pmol O2/[s ⋅ 1108 platelets]); bootstrap-boosted P 1α=0.04. The
study group also demonstrated lowered respiration in the ET-state (normalized for protein content): 12.31 (4.84) vs 16.48 (1.72) (pmol O2/[s ⋅ mg of protein]); bootstrap-boosted P 1α=0.049.
CONCLUSIONS: Our results suggest increased proton and electron leak and decreased electron transfer system capacity in platelets from chronic smoke-exposed animals. These observations may also indicate that platelets play an important role in the pathobiology of COPD and its comorbidities and may serve as a background for possible therapeutic targeting. However, these preliminary outcomes should be further validated in studies based on larger samples.