南方医科大学学报2024，Vol.44Issue(3)：523-532,10.DOI:10.12122/j.issn.1673-4254.2024.03.14
积雪草苷对离体大鼠胸主动脉的舒张作用及其机制
Effect of asiaticoside on systolic blood pressure and relaxation of isolated thoracic aorta of rats
摘要
Abstract
Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.关键词
积雪草苷/降压/舒张血管/钾通道/钙通道Key words
asiaticoside/lowering blood pressure/vasodilation of blood vessels/potassium channel/calcium channel引用本文复制引用
卢国庆,李馨月,康品方,唐碧,孙红燕,孙正宇,刘乐强,王磊,张宁宁,王宇航,何一鸣,纪佳慧..积雪草苷对离体大鼠胸主动脉的舒张作用及其机制[J].南方医科大学学报,2024,44(3):523-532,10.基金项目
国家自然科学基金(81970313) （81970313）
安徽省自然科学基金(2208085MH192) （2208085MH192）
安徽省临床医学研究转化项目(202304295107020087) （202304295107020087）
安徽省高校协同创新项目(GXXT-2020-019) （GXXT-2020-019）
安徽省高校优秀青年项目(2022AH030141) （2022AH030141）
蚌埠医学院研究生科研创新计划(Byycxz23040)Supported by National Natural Science Foundation of China(81970313). （Byycxz23040）
