虾青素对糖尿病大鼠血管内皮功能的保护作用及机制  

The protective effect and related mechanisms of astaxanthin on endothelial function in diabetic rats

作　　者：林清飞 王华军[2] 林静 陈祖医 许昌声[2] 黄丹琴 张丽 梁继兴[3] 

机构地区：[1]福建省武夷山市立医院心血管内科,福建武夷山354300 [2]福建医科大学附属第一医院、福建省高血压研究所 [3]福建省立医院内分泌科

出　　处：《中华高血压杂志》2015年第6期530-536,共7页Chinese Journal of Hypertension

基　　金：福建省自然科学基金(2011J01394)

摘　　要：目的探讨虾青素对糖尿病大鼠主动脉内皮功能障碍是否有保护作用以及可能的分子机制。方法 34只雄性Wistar大鼠中,随机取18只通过注射1%链脲佐菌素构建大鼠1型糖尿病模型。未成模的2只弃用。正常大鼠随机分为正常空白对照组(CON,n=8)和正常空白对照+高剂量(30mg/kg)虾青素组(CON+H-ASX,n=8);造模成功的糖尿病大鼠随机分为糖尿病组(DM,n=8)和糖尿病+高剂量(30mg/kg)虾青素组(DM+H-ASX,n=8)。测定主动脉的内皮功能。采用酶联免疫吸附试验(ELISA)法检测血清氧化型低密度脂蛋白(ox-LDL)水平;硫代巴比妥酸反应物法(TBARS)和黄嘌呤氧化酶法检测主动脉组织中丙二醛和超氧化物歧化酶(SOD)的活性;逆转录聚合酶链反应和Western blot检测主动脉凝集素样氧化型低密度脂蛋白受体1(LOX-1)和内皮型一氧化氮合酶(eNOS)mRNA和蛋白表达。结果糖尿病大鼠出现了过度氧化及内皮功能障碍,表现为血清ox-LDL和主动脉丙二醛水平上升[分别为(4.64±0.55)比(2.64±0.18)μg/dL;(3.38±0.22)比(2.04±0.27)nmol/mg pro;均P<0.05],乙酰胆碱内皮依赖性血管舒张反应受抑制,并且LOX-1mRNA及蛋白表达上升(P<0.01),eNOS mRNA及蛋白表达下降(P<0.01),经虾青素处理血清ox-LDL和主动脉丙二醛水平下降[分别为(2.96±0.25)比(4.64±0.55)μg/dL;(2.04±0.17)比(3.38±0.22)nmol/mg pro;均P<0.05],乙酰胆碱内皮依赖性血管舒张反应受抑制减轻,eNOS上调(P<0.01),LOX-1表达下降(P<0.01)。结论虾青素抑制ox-LDL及其受体的表达,上调eNOS的表达,减轻糖尿病大鼠血管内皮功能障碍。Objective To investigate protective effects of astaxanthin （ASX） on endothelial function of aortas in dia- betic rats and its possible molecular mechanisms involved. Methods Eighteen rats were randomly selected out of 34 male Wistar rats for constructing type 1 diabetes model by a single intraperitoneal injection of 1 % streptozotocin （STZ） ,in which 2 rats failed to induce diabetes were excluded. Normal Wistar rats were randomly divided into con trol group and control rats treated with ASX （30 mg/kg） group. Diabetic rats were randomly divided into diabetic group （n=8） and diabetic rats treated with ASX （30 mg/kg） group （n=8）. Endothelial function of aorta was ex- amined. Serum oxidized low-density lipoprotein（ox-LDL） level was detected by enzyme-linked immunosorbent assay （ELISA） ; the malondialdehyde level（MDA） and superoxide dismutase（SOD） activity in aorta by thiobarbituric acid reactive substance assay（TBARS） and xanthine oxidase methods respectively; and the mRNA and protein expression of lectin-like oxidized low-density lipoprotein receptor-1（ LOX-1） in aorta by reverse transcription polymerase chain reaction and Western blot methods. Results Excessive oxidative stress and endothelial dysfunction were found in STZ-induced diabetic rats as indicated by increased serum ox-LDL [（ 4.64 ± 0.55 ） vs （ 2.64± 0.18 ）μg/dL, P〈 0.05], increased aortic MDA [（3.38±0.22） vs （2.04±0.27） nmol/mg pro], and impaired endothelium dependentvasorelaxation to acetyleholine （Achl. Simultaneously, the mRNA and protein expression of LOX-1 were enhanced while eNOS expression reduced in the aortas of diabetic rats. ASX treatment could alleviate those manifestations by decreasing serum ox-LDL [（2.96±0.25） vs （4. 64±0.55）μg/dL, P〈0.01] and aortic MDA [（2. 04μ0.17） vs （3.38± 0.22） nmol/mg pro, P〈0.01], by improving endothelium-dependent vasodilator responses to ACh, and by upregulating eNOS while down-regulating LOX-1 expression. Conclusion

关 键 词：虾青素 糖尿病大鼠 凝集素样氧化型低密度脂蛋白受体1 内皮型一氧化氮合酶 内皮功能障碍 

分 类 号：R587.1[医药卫生—内分泌]