Pazhoohan Saeed, Raoufy Mohammad Reza, Javan Mohammad, Hajizadeh Sohrab
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
PLoS One. 2017 Oct 31;12(10):e0187249. doi: 10.1371/journal.pone.0187249. eCollection 2017.
Asthma represents an episodic and fluctuating behavior characterized with decreased complexity of respiratory dynamics. Several evidence indicate that asthma severity or control is associated with alteration in variability of lung function. The pathophysiological basis of alteration in complexity of breathing pattern in asthma has remained poorly understood. Regarding the point that Rho-kinase is involved in pathophysiology of asthma, in present study we investigated the effect of Rho-kinase inhibition on complexity of respiratory dynamics in a guinea pig model of asthma. Male Dunkin Hartley guinea pigs were exposed to 12 series of inhalations with ovalbumin or saline. Animals were treated by the Rho-kinase inhibitor Y-27632 (1mM aerosols) prior to each allergen challenge. We recorded respiration of conscious animals using whole-body plethysmography. Exposure to ovalbumin induced lung inflammation, airway hyperresponsiveness and remodeling including goblet cell hyperplasia, increase in the thickness of airways smooth muscles and subepithelial collagen deposition. Complexity analysis of respiratory dynamics revealed a dramatic decrease in irregularity of respiratory rhythm representing less complexity in asthmatic guinea pigs. Inhibition of Rho-kinase reduced the airway remodeling and hyperreponsiveness, but had no significant effect on lung inflammation and complexity of respiratory dynamics in asthmatic animals. It seems that airway hyperresponsiveness and remodeling do not significantly affect the complexity of respiratory dynamics. Our results suggest that inflammation might be the probable cause of shift in the respiratory dynamics away from the normal fluctuation in asthma.
哮喘表现为一种发作性且波动的行为，其特征是呼吸动力学复杂性降低。多项证据表明，哮喘的严重程度或控制情况与肺功能变异性的改变有关。哮喘中呼吸模式复杂性改变的病理生理基础仍知之甚少。鉴于 Rho 激酶参与哮喘的病理生理过程，在本研究中，我们在豚鼠哮喘模型中研究了 Rho 激酶抑制对呼吸动力学复杂性的影响。雄性 Dunkin Hartley 豚鼠接受 12 次卵清蛋白或生理盐水吸入。在每次过敏原激发前，用 Rho 激酶抑制剂 Y-27632（1mM 气雾剂）对动物进行治疗。我们使用全身体积描记法记录清醒动物的呼吸情况。暴露于卵清蛋白会引发肺部炎症、气道高反应性和重塑，包括杯状细胞增生、气道平滑肌厚度增加以及上皮下胶原沉积。呼吸动力学的复杂性分析显示，哮喘豚鼠的呼吸节律不规则性显著降低，表明其复杂性降低。抑制 Rho 激酶可减轻气道重塑和高反应性，但对哮喘动物的肺部炎症和呼吸动力学复杂性无显著影响。似乎气道高反应性和重塑对呼吸动力学复杂性没有显著影响。我们的结果表明，炎症可能是哮喘中呼吸动力学偏离正常波动的可能原因。
