■呼吸系统疾病中的性别特异性模式,比如哮喘,COPD,囊性纤维化,阻塞性睡眠呼吸暂停,特发性肺纤维化,以前都有记录。急性肺损伤(ALI)的动物模型提供了对性别差异的见解,与雌性小鼠相比,雄性小鼠表现出明显的肺水肿和血管渗漏。我们的实验室提供的证据表明,在博来霉素诱导的ALI恢复过程中,雄性大鼠的化学反射是致敏的。但ALI后是否发生基于性别的化学反射改变尚不清楚.为了弥合这个差距,本研究采用博来霉素诱导的ALI动物模型,研究ALI恢复过程中化学感受器反射激活的性别差异.
■使用单次气管内滴注博来霉素(bleo,2.5mg/Kg)(第1天)。在bleo前1-2天测量静息呼吸频率(fR),bleo后第7天(D7),和1个月(1个月)后bleo。使用全身体积描记术在bleo给药之前(bleo前)和bleo后1m测量对缺氧(10%O2,0%CO2)和常氧高碳酸血症(21%O2,5%CO2)的化学反射反应。呼吸暂停低通气指数(AHI),叹息后呼吸暂停,在每个时间点测量叹息。
■雄性和雌性大鼠在bleo前时间点的静息fR或在bleo后D7的静息fR增加没有显着差异。在bleo后1个月,两种性别的静息fR均部分恢复,但雄性大鼠的静息fR向正常范围的恢复显着降低。AHI,叹息后呼吸暂停,bleo前和bleo后1个月的雄性和雌性大鼠的叹息没有差异。然而,在D7后bleo,雄性大鼠的AHI高于雌性大鼠。雄性和雌性大鼠对缺氧和常氧高碳酸血症均表现出敏感的化学反射反应,两性之间没有显着差异。
■在ALI后出现静息通气参数的性别差异,雄性大鼠静息fR延长增加,AHI增大。另一方面,我们没有发现在bleo后1m时发生的化学反射致敏的任何性别差异。这项工作有助于更好地了解肺部疾病中基于性别的变化。
UNASSIGNED: Sex-specific patterns in respiratory conditions, such as asthma, COPD, cystic fibrosis, obstructive sleep apnea, and idiopathic pulmonary fibrosis, have been previously documented. Animal models of acute lung injury (ALI) have offered insights into sex differences, with male mice exhibiting distinct lung edema and vascular leakage compared to female mice. Our lab has provided evidence that the chemoreflex is sensitized in male rats during the recovery from
bleomycin-induced ALI, but whether sex-based chemoreflex changes occur post-ALI is not known. To bridge this gap, the current study employed the
bleomycin-induced ALI animal model to investigate sex-based differences in chemoreflex activation during the recovery from ALI.
UNASSIGNED: ALI was induced using a single intra-tracheal instillation of
bleomycin (bleo, 2.5 mg/Kg) (day 1). Resting respiratory frequency (fR) was measured at 1-2 days pre-bleo, day 7 (D7) post-bleo, and 1 month (1 mth) post-bleo. The chemoreflex responses to hypoxia (10% O2, 0% CO2) and normoxic-hypercapnia (21% O2, 5% CO2) were measured before bleo administration (pre-bleo) and 1 mth post-bleo using whole-body plethysmography. The apnea-hypopnea Index (AHI), post-sigh apneas, and sighs were measured at each time point.
UNASSIGNED: There were no significant differences in resting fR between male and female rats at the pre-bleo time point or in the increase in resting fR at D7 post-bleo. At 1 mth post-bleo, the resting fR was partially restored in both sexes but the recovery towards normal ranges of resting fR was significantly lower in male rats. The AHI, post-sigh apneas, and sighs were not different between male and female rats pre-bleo and 1 mth post-bleo. However, at D7 post-bleo, the male rats exhibited a higher AHI than female rats. Both male and female rats exhibited a sensitized chemoreflex in response to hypoxia and normoxic-hypercapnia with no significant differences between sexes.
UNASSIGNED: A sex difference in resting ventilatory parameters occurs post ALI with a prolonged increase in resting fR and larger AHI in male rats. On the other hand, we did not find any sex differences in the chemoreflex sensitization that occurs at 1 mth post-bleo. This work contributes to a better understanding of sex-based variations in lung disorders.