Mechanism Of The Relaxant Effect Of Clomipramine HCl On Mouse Airway Smooth Muscle

Asthma is a heterogeneous disease characterized by chronic airway inflammation and airway hyperresponsiveness.Patients often have dyspnea,paroxysmal chest tightness and cough,accompanied by wheezing and other symptoms.The incidence of asthma in the world is still on the rise.Asthma brings great threat to human health and is an urgent medical problem.Depression is one of the common comorbidities of asthma.Studies have shown that there are some common pathogenesis between the two diseases.Therefore,we wonder whether the drugs used to treat depression also improve asthma.Based on the previous screening and pre-experiment,we found that Clomipramine HCl relaxed the contracted trachea rings of mice.Clomipramine HCl is a tricyclic drug for depression and obsessive-compulsive disorder,and has not been reported for the relief or treatment of asthma.Therefore,we took Clomipramine HCl as the research object,deeply explored its mechanism of relaxation of airway smooth muscle in mice,and wish to provide a new idea for the treatment of asthma.We designed the following experiments:at the tissue level,tension transducers were used to explore the effects of drugs on the pre-contracted mice trachea ring.At the cellular level,the effect of drugs on ion channel currents in acute isolated mouse tracheal smooth muscle cells was detected by patch clamp technique.At the individual level,the effects of drugs on trachea and lung inflammation caused by asthma were observed by establishing asthma model.At the molecular level,RT-PCR was used to detect the effect of drugs on the expression of some inflammatory factors in mouse lung tissue.Experimental results showed that Clomipramine HCl could relax the abnormal contraction of tracheal smooth muscle caused by different agonists because it inhibited voltage-dependent calcium channel and non-selective cationic channel,reversed the regulation of Na⁺/Ca²⁺exchanger and enhanced the current of large conductance Ca²⁺-sensitive K⁺channel.However,Clomipramine HCl didn’t improve the inflammatory response caused by asthma well.It didn’t relieve asthma-induced bronchial wall thickening,inflammatory cell infiltration,and goblet cell proliferation,like dexamethasone.It also didn’t reduce the high expression of some inflammatory factors in the lung tissue of asthmatic mice.These results suggest that although Clomipramine HCl relaxes the isolated trachea ring,it is not an ideal treatment drug for asthma.