Mechanism Of Isoliquiritigenin Induced Vasodilation In Mice Mesenteric Arteies

Flavonoids are ubiquitous in fruits,vegetables,cereals and red wines and have proven to be highly effective and low toxic for a wide range of therapeutic activities.Studies have shown that flavonoids are associated with a reduced incidence of diseases such as stroke,coronary heart disease and cancer.Isoliquiritigenin is a flavonoid substance with a chalcone structure,which has vasodilation,anti-platelet aggregation and anti-allergy effects.Previous studies have shown that isoliquiritigenin has the effects of relaxing the aorta of rats and the basilar artery of rats,but the role of mesenteric arteries has not been reported.On this basis,the mechanism of action of isoliquiritigenin on the mesenteric artery of diastolic mice was carried out at the level of ex vivo organs,and the mechanism of action of isoliquiritigenin on smooth muscle cells was carried out at the cellular level.Provide reference for the basic research of isoliquiritigenin in diastolic blood vessels.The effect of isoliquiritigenin on the vascular ring tension of mesenteric artery in vitro.The in vitro isolated mesenteric artery vascular ring was used as a model to investigate the cumulative concentration of isoliquiritigenin?0.1,0.3,1,3,10,30,100?M?on the pre-contracted endothelial integrity of PE and the relaxation of the endothelium-free vascular ring.The endothelium-lowering factor was investigated for nitric oxide.Effect of prostacyclin on vasodilation;investigation of cumulative concentration of isoliquiritigenin?0.1-100?M?on the relaxation of KCl pre-contracted devascularized vascular rings;investigation of L-type calcium channel inhibitor nifedipine versus isoliquiritin the inhibitory effect of diastolic effect;the inhibitory effect of K⁺channel inhibitors TEA and ibtx on the relaxation of isoliquiritigenin was investigated.The effect of isoliquiritigenin on membrane potential of mouse mesenteric artery smooth muscle cells.Changes in membrane potential of smooth muscle cells were measured using a laser confocal microscope?LSCM?.The changes of membrane potential of smooth muscle cells by three concentrations of 0.1,10,100?M were investigated.The inhibitory effect of specific K⁺channel inhibitor ibtx on hyperpolarization of smooth muscle cells was investigated.The results showed:1.Isoliquiritigenin has a relaxing effect on the mesenteric artery vascular ring of mice,and the diastolic effect is more obvious with the increase of concentration,which is concentration-dependent.2.The diastolic effect of isoliquiritigenin is non-endothelium-dependent and has nothing to do with the endogenous vasodilators nitric oxide and prostacyclin.3,isoliquiritigenin has a significant relaxation effect on the devascularized vascular ring pre-contracted by KCl,indicating that isoliquiritigenin can relax the blood vessels by inhibiting Ca²⁺influx.4.L-type calcium channel inhibitor nifedipine pre-incubation of the vascular ring,the relaxation effect of isoliquiritigenin on the vascular ring was significantly reduced,indicating that the relaxation effect of isoliquiritigenin has the participation of L-type calcium channel,isoliquiritigenin can Inhibition of Ca²⁺influx by inhibition of VDCC.5.Non-specific BK_Ca channel inhibitor TEA pre-incubation of the vascular ring,can significantly reduce the role of vasodilation;further use of the specific BK_Ca channel inhibitor ibtx pre-incubation of the vascular ring,can also significantly reduce the relaxation of the vascular ring,and has significant Statistical significance.It is indicated that the relaxation effect of isoliquiritigenin depends on the BK_Ca channel.6.Isoliquiritigenin can darken the fluorescence intensity of smooth muscle cells and hyperpolarize cells.With the increase of the concentration of isoliquiritigenin,the hyperpolarization effect is more obvious,indicating that isoliquiritigenin can inhibit Ca²⁺influx.7.The specific BK_Ca channel inhibitor ibtx cause the hyperpolarization of smooth muscle cells,indicating that the relaxation effect of isoliquiritigenin has the participation of K⁺channel.