褐藻寡糖对N^(G)-硝基-L-精氨酸甲酯诱导小鼠高血压的改善作用

Ameliorative Effect of Alginate Oligosaccharides on N^(G)-Nitro-L-arginine methyl ester-Induced Hypertension in Mice

目的:研究褐藻寡糖(alginate oligosaccharide,AOS)对N^(G)-硝基-L-精氨酸甲酯(N^(G)-nitro-L-arginine methyl ester,L-NAME)诱导小鼠高血压的改善作用及其机制。方法:采用AOS预防性干预高血压小鼠6周,监测小鼠血压,观察小鼠肾脏、心脏和主动脉组织病理形态学变化并测定其氧化应激水平及血清中总抗氧化能力、一氧化氮、血管紧张素II和内皮素-1等水平,同时检测主动脉中内皮型一氧化氮合成酶(endothelial nitric oxide synthase,eNOS)蛋白表达情况。结果:给药1.5 g/kg AOS能够有效降低L-NAME诱导高血压小鼠的收缩压(22.4 mmHg),明显改善肾脏、心脏和主动脉的组织形态,减轻氧化应激损伤;血清中尿素氮、肌酐、尿酸、乳酸脱氢酶、肌酸激酶、血管紧张素II和内皮素-1水平比模型组小鼠分别降低38.0%、46.5%、45.2%、15.9%、46.4%、29.5%和26.2%,而总抗氧化能力和一氧化氮浓度分别提高24.1%和246.5%;主动脉中eNOS蛋白表达显著增加152.9%。结论:AOS对小鼠具有降血压作用,能够抑制高血压诱发的氧化应激和改善血管内皮功能障碍,本研究可为将AOS作为抗高血压功能食品配料提供科学依据。

Objective:To study the ameliorative effect and mechanism of alginate oligosaccharides(AOS)on N^(G)-nitro-Larginine methyl ester(L-NAME)-induced hypertension in mice.Methods:AOS was used as a preventive treatment for hypertensive mice for 6 weeks.Blood pressure of the mice was monitored,pathological changes in kidney,heart and aortic tissues were observed and the level of oxidative stress was measured.Furthermore,serum levels of total antioxidant capacity(TAC),nitric oxide,angiotensin II,and endothelin-1 were measured,and the protein expression of endothelial nitric oxide synthase(eNOS)in the aorta was also detected.Results:AOS(1.5 g/kg body weight)effectively reduced the systolic blood pressure value of 22.4 mmHg in L-NAME-induced hypertensive mice,and significantly ameliorated pathological changes and oxidative stress injury in the kidney,heart and aorta.Compared with the model group,the serum levels of blood urea nitrogen,creatinine,uric acid,lactate dehydrogenase activity,creatine kinase activity,angiotensin II and endothelin-1 in AOS-treated mice were reduced by 38.0%,46.5%,45.2%,15.9%,46.4%,29.5%,and 26.2%,respectively,and serum TAC and nitric oxide concentration were increased by 24.1%and 246.5%,respectively.Furthermore,the protein expression of eNOS in the aorta was significantly increased by 152.9%.Conclusion:AOS has a hypotensive effect in mice,which can inhibit oxidative stress and ameliorate vascular endothelial dysfunction induced by hypertension.This study provides a scientific basis for the potential of AOS as a functional food ingredient for antihypertension.