Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin Medical University, PR China.
Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin Medical University, PR China.
Eur J Pharmacol. 2019 Jun 15;853:229-235. doi: 10.1016/j.ejphar.2019.03.047. Epub 2019 Mar 29.
Our previous study found that the anthelmintic drug niclosamide relaxed the constricted arteries and inhibited proliferation and migration of vascular smooth muscle cells. Here, we investigated the effect of niclosamide ethanolamine (NEN) on trachea function and the proliferation and migration of trachea smooth muscle cells. Isometric tension of trachea was recorded by multi-channel myograph system. The cell proliferation was detected by using BrdU cell proliferation assay. The cell migration ability was evaluated by using scratch assay. The protein level was measured by using western blot technique. Acute treatment with NEN dose-dependently relaxed acetylcholine chloride (Ach)- and High K physiological salt solution (KPSS)-induced constriction of mice trachea. Pre-treatment with NEN inhibited Ach- and KPSS-induced constriction of mice trachea. NEN treatment inhibited proliferation of human bronchial smooth muscle cells (HBSMCs), inhibited migration of HBSMCs and rat primary trachea smooth muscle cells. NEN treatment activated adenosine monophosphate activated protein kinase (AMPK) activity and inhibited signal transducer and activator of transcription 3 (STAT3) activity in HBSMCs. In conclusion, niclosamide ethanolamine induces trachea relaxation and inhibits proliferation and migration of trachea smooth muscle cells, indicating that niclosamide might be a potential drug for chronic asthma treatment.
我们之前的研究发现，驱虫药尼氯硝唑能使收缩的动脉松弛，并抑制血管平滑肌细胞的增殖和迁移。在这里，我们研究了尼氯硝唑乙醇胺（NEN）对气管功能以及气管平滑肌细胞增殖和迁移的影响。多通道肌描记系统记录气管的等长张力。BrdU 细胞增殖试验检测细胞增殖。划痕试验评估细胞迁移能力。通过 Western blot 技术测量蛋白水平。急性处理 NEN 可剂量依赖性地松弛氯化乙酰胆碱（Ach）和高钾生理盐溶液（KPSS）诱导的小鼠气管收缩。NEN 预处理抑制 Ach 和 KPSS 诱导的小鼠气管收缩。NEN 处理抑制人支气管平滑肌细胞（HBSMC）的增殖，抑制 HBSMC 和大鼠原代气管平滑肌细胞的迁移。NEN 处理激活人支气管平滑肌细胞中的单磷酸腺苷激活蛋白激酶（AMPK）活性并抑制信号转导和转录激活因子 3（STAT3）活性。总之，尼氯硝唑乙醇胺诱导气管松弛并抑制气管平滑肌细胞的增殖和迁移，表明尼氯硝唑可能是治疗慢性哮喘的潜在药物。
