中国药理学与毒理学杂志2025，Vol.39Issue(4)：260-267,8.DOI:10.3867/j.issn.1000-3002.2025.04.003
二甲基亚砜对离体大鼠主动脉和肾内动脉的舒张作用及其机制
Vasodilatory effect of dimethyl sulfoxide on aortic and intrarenal arteries of rats and its mechanisms
摘要
Abstract
OBJECTIVE To investigate the vasodilatory effect of dimethyl sulfoxide(DMSO)on isolated aortic arteries and intrarenal arteries of rats and the mechanisms.METHODS ① Rat aortas and intrarenal arteries were pre-contracted with KCl 60 mmol·L-1,U46619 0.3 μmol·L-1 or PE 3 μmol·L-1.Following equilibration,dimethyl sulfoxide(DMSO)was cumulatively administered at concentrations of 0.1%,0.3%,1.0%,3.0%and 10.0%.Changes in the vascular tension of aortic and intrarenal arterial rings were recorded using an isolated vessel tension measurement system.Rat intrarenal arteries were pre-contracted with KCl 60 mmol·L-1,U46619 0.3 μmol·L-1 or PE 3 μmol·L-1.Cumulative additions of DMSO(3.0%and 10.0%)were administered as the control group.Following pre-contraction with each of the three stimulants,the voltage-gated potassium channel(Kv)inhibitor 4-AP(0.5 mmol·L-1)was incubated for 15 min.Cumulative additions of DMSO(3.0%and 10.0%)were then administered,and the vascular relaxation percentages induced by DMSO before and after treatment were calculated.Whole-cell patch-clamp recordings were performed on acutely isolated intrarenal arterial smooth muscle cells of rat to assess Kv currents during cumulative DMSO applications(0.1%,0.3%,1.0%and 3.0%).② Rat aortic smooth muscle cells(A7r5)were exposed to DMSO concentration of 0.0%(control),0.1%,0.3%,1.0%and 3.0%for 24 h.Intracellular reactive oxygen species(ROS)levels were detected using the DCFH-DA fluorescent probe.Malondialdehyde(MDA)content,catalase(CAT)activity,and superoxide dismutase(SOD)activity in A7r5 cells were measured by chemical colorimetry.Mitochondrial membrane potential was evaluated using the JC-1 fluorescent probe.RESULTS ① DMSO(0.1%-10.0%)dose-dependently relaxed rats aortic and intrarenal arteries pre-contracted with either KCl 60 mmol·L-1,U46619 0.3 μmol·L-1 or PE 3 μmol·L-1.The values of maximum relaxation were(42.3±9.7)%,(73.2±8.4)%,(99.2±4.7)%and(84.0±1.9)%,(80.5±6.1)%and(81.2±4.4)%,respectively.Compared with the control group,vasorelaxation of DMSO on IRAs precontracted with U46619 was significantly attenuated by Kv inhibitor 4-AP.② Low concentrations(0.1%and 0.3%)of DMSO significantly increased Kv currents,while high concentrations(1.0%and 3.0%)of DMSO significantly decreased Kv currents.High concentrations(1.0%and 3.0%)of DMSO remarkablely increased ROS and MDA levels,but significantly decreased CAT activity,SOD activity and mitochondrial membrane potential in A7r5 cells.CONCLUSION DMSO(0.1%-10.0%)can relax rats aortal and intrarenal arteries in a concentra-tion-dependent manner,and the mechanism may be related to Kv,oxidative stress and mitochondrial damage.关键词
二甲基亚砜/主动脉/肾内动脉/血管舒张/电压依赖性钾通道Key words
dimethyl sulfoxide/aortic arteries/renal arteries/vasorelaxing/voltage-activated potas-sium channel分类
医药卫生引用本文复制引用
吴超,杨晓敏,徐小佳,时晓婉,刘宇,张明升..二甲基亚砜对离体大鼠主动脉和肾内动脉的舒张作用及其机制[J].中国药理学与毒理学杂志,2025,39(4):260-267,8.基金项目
山西省留学回国人员科技活动择优资助项目(20210043) Shanxi Province Returned Overseas Personnel Science and Technology Activities Preferential Funding Project(20210043) （20210043）
