Relaxation Effect Of Repaglinide And Dictamnime On Airway Smooth Muscle In Mice

Asthma is a common and frequently-occurring disease in China.It is based on chronic airway inflammation and is mainly by airway obstruction,airway hyperresponsiveness and airway remodeling.Airway smooth muscle is the key structure and effector cells of the airway.It can produce contractile responses and secrete a variety of cellular mediators.It is an important target for studying the pathogenesis of asthma and the development of new drugs.In recent years,the"new use of old drugs"has become a hot spot in drug development.Through extensive literature search and preliminary experimental screening,we found that repaglinide and dictamnine have the ability to relax airway smooth muscle.Repaglinide is a short-acting insulin secretagogue,and also has the effects of relaxing blood vessels,anti-cancer,anti-inflammatory,and anti-oxidative stress.Dictamnine is a small molecule alkaloid with anti-inflammatory,anti-fungal,anti-angiogenic and anti-cancer activities.This study took airway smooth muscles as the target and explored the effects and mechanisms of repaglinide and dictamnine on diastolic trachea spasm,in order to screen new bronchodilators.A series of experiments were performed to explore the mechanism of these two drugs.At the tissue level,muscle tension measurement experiments were conducted to detect the effect of drugs on tracheal tension in BALB/c mice.At the cellular level,patch clamp experiments were performed using acutely isolated airway smooth muscle cells to detect changes in the ion channel current of the drug;MTT was used to detect the effect of the drug on the cell viability of A549 cells.At the living level,the effects of drugs on the respiratory resistance of living mice were investigated by a pulmonary function meter.The results showed that repaglinide and dictamnine inhibited the tracheal precontraction induced by high potassium solution or acetylcholine in a dose-dependent manner.The experimental results show that repaglinide and dictamnine have the ability to relax the abnormal contraction of airway smooth muscle cells,which is achieved by inhibiting voltage dependent calcium channel and non-selective cation channel mediated external calcium influx,reversely regulating Na⁺/Ca²⁺exchange,and enhancing the effects of potassium ion channels.In addition,repaglinide has a controllable effect on tissues and cells,and has high safety,which also can reduce airway resistance in living mice after atomization.Atomization can reduce airway resistance in living mice.These results suggest that repaglinide and dictamnine have calcium antagonistic effects on airway smooth muscle cells,reduce asthma symptoms,so both of them have the potential to be bronchodilators.