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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 whether astaxanthin has a protective effect on endothelial dysfunction in diabetic aorta and its possible molecular mechanism. Methods Totally 18 male Wistar rats were randomly divided into the model of type 1 diabetes mellitus induced by streptozotocin (STZ) injection. Unmolded 2 discarded. Normal rats were randomly divided into normal blank control group (CON, n = 8) and normal blank control + high dose (30mg / kg) astaxanthin group (CON + H-ASX, n = 8) Rats were randomly divided into diabetic group (DM, n = 8) and diabetic + high dose (30mg / kg) astaxanthin group (DM + H-ASX, n = 8). Aortic endothelial function was measured. Serum levels of oxidized low-density lipoprotein (ox-LDL) were measured by enzyme-linked immunosorbent assay (ELISA); TBARS and xanthine oxidase were used to detect the level of ox Aldehyde and superoxide dismutase (SOD) were determined by enzyme-linked immunosorbent assay (ELISA). The expressions of LOX-1 and endothelial nitric oxide synthase (eNOS) mRNA and protein expression. Results Overexpression and endothelial dysfunction were found in diabetic rats. The levels of serum ox-LDL and aortic malondialdehyde increased (4.64 ± 0.55 vs 2.64 ± 0.18 μg / dL, 3.38 ± 0.22, (2.04 ± 0.27) nmol / mg pro (all P <0.05). The acetylcholine endothelium-dependent vasorelaxation was inhibited and the mRNA and protein expressions of LOX-1 were increased (P <0.01) (2.96 ± 0.25) vs (4.64 ± 0.55) μg / dL respectively; (2.04 ± 0.17) vs (3.38 ± 0.22) nmol / mg pro; both P <0.05]. The inhibition of endothelium-dependent vasorelaxation was attenuated by echocardiography. The eNOS expression was up-regulated and the expression of LOX-1 was decreased (P <0.01). Conclusion Astaxanthin can inhibit the expression of ox-LDL and its receptor, up-regulate the expression of eNOS, and alleviate the vascular endothelial dysfunction in diabetic rats.