本研究拟探究血根碱对大鼠气道平滑肌细胞（rASMCs）的刚度、牵张力、应力纤维分布等细胞生物力学特性的影响。体外培养的 rASMCs 经过血根碱溶液在不同浓度（0.005～5 μmol/L）条件下分别处理 12 h、24 h、36 h 和 48 h 后，采用噻唑盐比色法、光学磁粒扭转细胞测量仪、傅里叶变换牵张力显微术、划痕实验和免疫荧光显微技术等检测其活性、刚度、牵张力、迁移速度和微丝骨架分布等细胞生物力学特性的变化。实验结果显示，在浓度低于 0.5 μmol/L 时，血根碱对细胞活性没有明显影响，但对细胞生物力学特性呈现浓度和时间依赖性，具体表现为 rAMSCs 经 0.05 μmol/L 和 0.5 μmol/L 浓度的血根碱处理 12 h 和 24 h 后细胞刚度、细胞牵张力和细胞迁移速度均明显降低、细胞骨架应力纤维出现解聚。鉴于气道平滑肌细胞（ASMCs）生物力学特性在哮喘气道高反应性（AHR）中的关键作用，上述的实验结果提示，血根碱有可能通过改变气道平滑肌细胞生物力学特性而改善 AHR，进而为开发基于血根碱的气道松弛剂等哮喘治疗药物奠定基础
References
[1]
1. Mccracken J L, Veeranki S P, Ameredes B T, et al. Diagnosis and management of asthma in adults: a review. JAMA, 2017, 318(3): 279-290.
[2]
2. Rydell-T？rm？nen K, Risse P A, Kanabar V, et al. Smooth muscle in tissue remodeling and hyper-reactivity: airways and arteries. Pulm Pharmacol Ther, 2013, 26(1): 13-23.
[3]
3. Chapman D G, Irvin C G. Mechanisms of airway hyper-responsiveness in asthma: the past, present and yet to come. Clinical and Experimental Allergy, 2015, 45(4): 706-719.
[4]
4. Bates J H, Maksym G N. Mechanical determinants of airways hyperresponsiveness. Crit Rev Biomed Eng, 2011, 39(4): 281-296.
[5]
5. Ozier A, Allard B, Bara I, et al. The pivotal role of airway smooth muscle in asthma pathophysiology. J Allergy (Cairo), 2011: 742710.
[6]
6. Affonce D A, Lutchen K R. New perspectives on the mechanical basis for airway hyperreactivity and airway hypersensitivity in asthma. J Appl Physiol (1985), 2006, 101(6): 1710-1719.
[7]
7. Janssen L J. Airway smooth muscle as a target in asthma and the beneficial effects of bronchial thermoplasty. J Allergy (Cairo), 2012: 593784.
[8]
8. Camoretti-Mercado B. Targeting the airway smooth muscle for asthma treatment. Transl Res, 2009, 154(4): 165-174.
[9]
10. Stephens N L, Li Weilong, Jiang He, et al. The biophysics of asthmatic airway smooth muscle. Respir Physiol Neurobiol, 2003, 137(2/3): 125-140.
[10]
11. Black J L, Panettieri R A, Banerjee A, et al. Airway smooth muscle in asthma: just a target for bronchodilation?. Clin Chest Med, 2012, 33(3): 543-558.
[11]
12. Oria R, Wiegand T, Escribano J, et al. Force loading explains spatial sensing of ligands by cells. Nature, 2017, 552(7684): 219-224.
[12]
13. Dinardo C L, Santos H C, Vaquero A R, et al. Smoking and female sex: independent predictors of human vascular smooth muscle cells stiffening. PLoS One, 2015, 10(12): e0145062.
[13]
14. Trepat X, DENG Linhong, An S S, et al. Universal physical responses to stretch in the living cell. Nature, 2007, 447(7144): 592-595.
[14]
17. Park C Y, Zhou E H, Tambe D, et al. High-throughput screening for modulators of cellular contractile force. Integr Biol (Camb), 2015, 7(10): 1318-1324.
[15]
18. Hu C M, Cheng H W, Cheng Y W, et al. Mechanisms underlying the induction of vasorelaxation in rat thoracic aorta by sanguinarine. Jpn J Pharmacol, 2001, 85(1): 47-53.
[16]
20. Wang Hui, Yin G, Yu Chunhong, et al. Inhibitory effect of sanguinarine on PKC-CPI-17 pathway mediating by muscarinic receptors in dispersed intestinal smooth muscle cells. Res Vet Sci, 2013, 95(3): 1125-1133.
[17]
22. Zhang Ying, Ng S S, Wang Yilei, et al. Collective cell traction force analysis on aligned smooth muscle cell sheet between three-dimensional microwalls. Interface Focus, 2014, 4(2): 20130056.
[18]
23. An S S, Fabry B, Trepat X, et al. Do biophysical properties of the airway smooth muscle in culture predict airway hyperresponsiveness?. Am J Respir Cell Mol Biol, 2006, 35(1): 55-64.
[19]
24. Seow C Y. Passive stiffness of airway smooth muscle: the next target for improving airway distensibility and treatment for asthma?. Pulm Pharmacol Ther, 2013, 26(1): 37-41.
9. Zuyderduyn S, Sukkar M B, Fust A, et al. Treating asthma means treating airway smooth muscle cells. Eur Respir J, 2008, 32(2): 265-274.
[22]
15. Rosner S R, Pascoe C D, Blankman E, et al. The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics. PLoS One, 2017, 12(3): e0171728.
[23]
16. Deshpande D A, Wang W C H, Mcilmoyle E L, et al. Bitter taste receptors on airway smooth muscle bronchodilate by a localized Calcium flux and reverse obstruction. Nat Med, 2010, 16(11): 1299-1304.
21. Wang Yue, Lu Yun, Luo Mingzhi, et al. Evaluation of pharmacological relaxation effect of the natural product naringin on in vitro cultured airway smooth muscle cells and in vivo ovalbumin-induced asthma Balb/c mice. Biomedical reports, 2016, 5(6): 715-722.
