姜黄素诱导急性高脂血症大鼠动脉核因子E2相关因子2表达

Curcumin Induces the Expression of Nuclear Factor E-2-Related 2 on Aorta of Rats with Acute Hyperlipidemia

目的观察姜黄素对急性高脂血症大鼠血脂、血管内皮功能及氧化应激状态的影响,探讨其抗氧化作用与核因子E2相关因子2(Nrf2)表达水平的关系。方法将雄性SD大鼠随机分为5组,即正常对照组、高脂组、姜黄素低剂量组[125 mg/(kg·d)]、姜黄素高剂量组[250 mg/(kg·d)]、阿托伐他汀组[(2.1 mg/(kg·d)]。正常对照组、高脂组用给药溶质玉米油预处理,其他组用相应药物预处理。预处理10天后采用腹腔注射蛋黄乳液的方法建立急性高脂血症大鼠模型,腹腔注射24 h后测定血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)、氧化型低密度脂蛋白(ox-LDL)、一氧化氮(NO)、超氧化物歧化酶(SOD)活力,同时留取主动脉组织测定丙二醛(MDA)含量及行病理学检查。结果与正常对照组比较,高脂组TC、TG、LDLC、ox-LDL、MDA和Nrf2的表达升高,SOD活力、NO含量降低。与高脂组比较,高、低剂量姜黄素组及阿托伐他汀组TC、TG、ox-LDL、MDA降低,Nrf2、SOD活力、NO含量增加。高剂量姜黄素组上述作用优于低剂量姜黄素组。结论姜黄素通过降低血脂及诱导Nrf2的表达,提高主动脉的抗氧化能力,发挥内皮保护作用。

Aim To observe the effects of curcumin on blood lipid,endothelial function and oxidative stress of acute hyperlipidemia model rats,and to investigate the relationship between antioxidative effect and the expression of nuclear factor E-2-related 2（ Nrf2）. Methods Fourty healthy male Sprague Dawley rats were randomly divided into normal control group,hyperlipidemia model group,high-dose curcumin group（ 250 mg/（ kg · d））,low-dose curcumin group（ 125 mg/（ kg·d）） and atorvastatin intervention group（ 2. 1 mg/（ kg·d））. The rats in normal control group and hyperlipidemia model group were gavaged with corn oil,rats in other groups were gavaged with high dose curcumin,low dose curcumin and atorvastatin respectively for 10 days. The acute hyperlipidemia model was established by intraperitoneal injection of yolk emulsion 1 hour after the last gavage. Serum total cholesterol（ TC）,triglyceride（ TG）,low density lipoprotein cholesterol（ LDLC）,oxygenized low density lipoprotein（ ox-LDL）,nitric oxide（ NO）,superoxide dismutase（ SOD）activity were measured 24 hours after intraperitoneal injection,while malondialdehyde（ MDA） content and pathological examination of aorta tissue were determined. Results Compared with the normal control group,the serum TC,TG,LDLC and ox-LDL increased in the rats of model group; SOD activity and NO content reduced,MDA content and expression of Nrf2 in the aorta tissue increased. Compared with the model group,serum TC,TG,ox-LDL and MDA content of aorta tissue was obviously decreased in high-dose curcumin group,low-dose curcumin group and atorvastatin intervention group,serum SOD activity,NO level and Nrf2 expression in aorta tissue increased. Conclusion Curcumin may play the role of endothelial protection through improving the antioxidant capacity of the aorta by lowering blood lipid and inducing the expression of Nrf2.