青蒿琥酯对小鼠气道阻力及气道平滑肌牵张力的效应研究

The Effect of Artesunate on Murine Airway Resistance and Airway Smooth Muscle Cell Traction Force

青蒿琥酯是著名的抗疟药青蒿素的衍生物,可抑制哮喘动物的气道炎症,但其对气道阻力及平滑肌牵张力是否有影响未知。因此,首先建立了小鼠哮喘动物模型,通过肺功能仪检测青蒿琥酯对小鼠气道阻力的影响,并体外进行了小鼠气道平滑肌的分离培养,运用傅里叶变换牵张力显微术(FTTC)检测了青蒿琥酯对气道平滑肌牵张力的效应,并初步探讨了机制。结果显示,青蒿琥酯能有效降低哮喘小鼠的气道阻力,并呈现剂量依赖性,且120μg青蒿琥酯对降低气道阻力的程度相当于3μg沙丁胺醇(常规哮喘治疗)的效果;青蒿琥酯可降低气道平滑肌细胞的牵张力,并使胞内[Ca^(2+)]i增加。表明青蒿琥酯是一种经济的、潜在的支气管舒张剂,为支气管哮喘的治疗提供新的前景。

Artesunate is a derivative of the well-known anti-malarial drug,artemisinin.It has been shown to inhibit airway inflammation in animal models of asthma,but is yet to be studied for its effect on airway resistance（Raw） and airway smooth muscle cell（ASMC） traction force.Since Raw and ASMC traction force are key elements in the pathogenesis and treatment of asthma,we thus evaluated the effect of artesunate on Raw and ASMC traction force with experimental mouse model of asthma.Mouse model of asthma was established by ovalbumin sensitization and challenge,and then tested for Raw w/o administration of artesunate at given dosage.On the other hand,ASMCs were harvested from the mouse lung and cultured in vitro.Subsequently,the in vitro cultured ASMCs were tested for traction force by using Fourier Transform Traction Force Cytometry（FTTC） in the absence or presence of artesunate.The results showed that artesunate dose dependently reduced Raw of the asthma mouse models,and 120μg artesunate was comparable to 3μg salbutamol（conventional asthma therapy） in effect of Raw reduction.Artesunate also attenuated traction force generated by in vitro ASMCs,together with increase of intracellular calcium concentration（[Ca^（2＋）]i）.These results suggest that artesunate may be an inexpensive potential airway dilator,which provides new drug alternative choice for treating bronchial asthma.