Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
Clinics (Sao Paulo). 2011;66(8):1451-6. doi: 10.1590/s1807-59322011000800024.
To study the effects of mycophenolate sodium on mucociliary clearance.
Mycophenolate is one of the most commonly used immunosuppressive drugs in lung transplantation. Although its pharmacokinetic properties are well defined, its side effects on mucociliary clearance have not yet been studied.
Sixty rats were subjected to left bronchial section and anastomosis. The right bronchus was used as a control. After surgery, the rats were assigned to two groups based on whether they received saline solution (n = 30) or mycophenolate sodium (n = 30). After 7, 15, or 30 days of treatment, 10 animals from each group were sacrificed, and in vitro mucus transportability, in situ mucociliary transport velocity and ciliary beat frequency were measured.
The analysis of mucus transportability revealed that neither mycophenolate nor bronchial section altered any transportability related property for up to 30 days of treatment after surgery (p>0.05). With regard to ciliary beat frequency, the operated left bronchi from the mycophenolate group showed a significant decrease on post-surgical day 30 (p = 0.003). In addition, we found a significant reduction in the in situ mucociliary transport velocity in the mycophenolate-treated group (p = 0.0001).
These data add important information regarding mucociliary clearance dysfunction following mycophenolate therapy and suggest that mycophenolate might contribute to the high incidence of respiratory tract infections in lung transplant patients. Further studies are needed to investigate the combined action of mycophenolate with other immunosuppressive drugs and to establish methods to protect and recover mucociliary clearance, an important airway defense mechanism.
研究吗替麦考酚酯钠对黏液纤毛清除功能的影响。
吗替麦考酚酯是肺移植中最常用的免疫抑制剂之一。尽管其药代动力学特性已得到充分研究，但尚未研究其对黏液纤毛清除功能的副作用。
60 只大鼠行左侧支气管切断和吻合术。右侧支气管作为对照。手术后，根据是否接受生理盐水溶液（n = 30）或吗替麦考酚酯钠（n = 30）治疗，将大鼠分为两组。每组 10 只大鼠分别于治疗后 7、15 或 30 天处死，测量体外黏液传输能力、原位黏液纤毛传输速度和纤毛摆动频率。
分析黏液传输能力的结果显示，在手术后长达 30 天的治疗期间，无论是吗替麦考酚酯还是支气管切开都没有改变任何与传输能力相关的特性（p>0.05）。关于纤毛摆动频率，来自吗替麦考酚酯组的左侧手术支气管在手术后第 30 天显示出显著降低（p = 0.003）。此外，我们发现吗替麦考酚酯治疗组的原位黏液纤毛传输速度显著降低（p = 0.0001）。
这些数据为吗替麦考酚酯治疗后黏液纤毛清除功能障碍提供了重要信息，并提示吗替麦考酚酯可能导致肺移植患者呼吸道感染的高发生率。需要进一步研究来调查吗替麦考酚酯与其他免疫抑制剂的联合作用，并建立保护和恢复黏液纤毛清除功能的方法，这是一种重要的气道防御机制。
