Role Of Morin In Vascular Endothelial Cell Function

Hypertension is the most common cardiovascular disease in China,and its essence is microcirculatory disorder.The increase in blood pressure is based on an increase in peripheral resistance,and the change of resistance vascular function promotes the occurrence and development of hypertension.Endothelial cells are particularly important for maintaining vascular function,and endothelial injury leads to vascular dysfunction,which causes an increase in blood pressure.At present,hypertension patients mainly control blood pressure by taking antihypertensive drugs,but these drugs have limitations in maintaining blood pressure stability.Studies have found that flavonoids have the effect on lowering blood pressure.Morin has been reported to have anti-inflammatory,anti-oxidative and anti-apoptotic effects.However,the effect of morin on vascular endothelial cell function remains to be further explored.This study explored its effect in hypertension from studing the role of morin in resistance vascular function and endothelial cell injury caused by inflammation.The main results are as follows:1.The effects of morin on vascular function of isolated rat mesenteric arteries were examined by myography,found that morin induced vascular relaxation in a concentration-dependent manner.Morin also concentration-dependent induced mesenteric arteries relaxation in?N^?-Nitro-L-arginine methyl ester hydrochloride,L-NAME?-induced hypertension rats.Morin co-incubated with the isolated mesenteric arteries of L-NAME-induced hypertensive rats significantly increased the acetylcholine-mediated vasodilation.Through feeding L-NAME-induced hypertensive rats under a given dose of morin,we found that morin reduced the blood pressure and improved acetylcholine-mediated relexation response on mesenteric arteries.2.Resistance vessels play an important role in the control of blood pressure.Endothelium-derived hyperpolarizing factor?EDHF?is a key pathway mediating resistance vessels vasodilation by causing hyperpolarization of endothelial cells to mediate vasodilation.Activation of the transient receptor potential vanilloid?TRPV4?channel in endothelial cell causes Ca²⁺influx to mediate EDHF response.The study of vascular tone revealed that morin endothelium-dependent induced relaxation of isolated rat mesenteric arteries.Subsequently,it was demonstrated that morin induces vasodilation by activating TRPV4 channel to induce endothelial Ca²⁺influx at the ex vivo vascular and cellular levels.The increase in intracellular Ca²⁺concentration through TRPV4 channel activates the small conductance Ca²⁺activated K⁺channel?SK?which is involved in the EDHF mechanism.It revealed that SK channels were involved in morin-induced endothelium-dependent relexation of isolated rat mesenteric arteries by myography experiment.By studying the changes of K⁺and cell polarization in primary mesenteric artery endothelial cells,it was found that morin caused K⁺efflux and hyperpolarization of primary mesenteric artery endothelial cells by activating TRPV4 and SK channels.3.The occurrence of hypertension is often accompanied by an increase of inflammation.Inflammation could induce endothelial cells injury and affect the normal function of endothelial cells.Since morin has an anti-inflammatory and anti-oxidative effect,this study investigated the effect of morin on inflammation-induced endothelial injury in vitro.Cell viability assay showed that oxidized low-density lipoprotein?ox-LDL?can significantly reduce the cell viability of human umbilical vein endothelial cells?HUVECs?,improved by treatment of morin.Ox-LDL significantly inhibited the cell migration ability,increased cellular oxidative stress and the expression of inflammatory factors level that induced HUVECs injury.The injury caused by ox-LDL to HUVECs was significantly alleviated by morin,indicating that morin has protective effect on HUVECs.4.Autophagy is a cytoprotective mechanism under stress,and it has been found that natural compounds can protect cardiovascular cells by inducing autophagy.In this study,the protective effect of morin on endothelial cells was explored by analyzing the expression of autophagy-related proteins and signaling.The results showed that,morin acting on ox-LDL-treated HUVECs significantly increased the expression of LC3 and decreased the expression of p62,indicating that morin treatment increased autophagy level.Autophagy inhibitor chloroquine?CQ?could significantly inhibit the cell migration ability;increase the level of cellular oxidative stress and inflammatory factors of HUVECs.Inhibit autophagy by CQ could reverse the protective effect of morin on HUVECs.By investigating the signaling pathway involved in autophagy,found that the expression of p-AMPK was increased and the expression of p-mTOR was decreased under morin treatment,indicating that the AMPK signaling pathway was activated by morin.AMPK inhibitor Compoud C?CC?inhibited AMPK signaling,morin-induced autophagy and reversed the protective effect of morin on HUVECs.It is indicated that morin-induced autophagy by activating AMPK signaling pathway mediates the protective effect on HUVECs.