番茄红素对高脂血症模型大鼠脑血管和神经元的保护作用

目的研究番茄红素对高脂血症所致脑血管和神经元损伤的保护作用。方法 SD大鼠在饲喂高脂饮食的同时每天ig给予番茄红素5,25,45,65,85,105和125 mg·kg-1,同时设正常对照组、高脂模型组和氟伐他汀钠10 mg·kg-1组,实验期4周。用试剂盒检测血清和脑总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、氧化型低密度脂蛋白(Ox-LDL)、总抗氧化能力(T-AOC)、白细胞介素1(IL-1)、肿瘤坏死因子α(TNF-α)、血管细胞黏附分子1(VCAM-1)、血管内皮生长因子(VEGF)和一氧化氮(NO)水平;Western蛋白印迹法检测脑组织密封蛋白5、胶质纤维酸性蛋白(GFAP)和磷酸化P38蛋白(p-P38)水平;尼氏染色观察海马CA1和CA3区神经元形态变化并对其计数;高效液相色谱法检测血清番茄红素浓度。结果实验第4周末,与高脂模型组相比,番茄红素25~85 mg·kg-1组血清和脑TC,TG,LDL-C,Ox-LDL,IL-1,TNF-α,VCAM-1,VEGF及脑NO,GFAP,p-P38水平降低(P<0.01),血清T-AOC,NO及脑密封蛋白5水平和脑海马区神经元数升高(P<0.01),105和125 mg·kg-1组仅血清TC,TG,LDL-C及血清和脑IL-1,TNF-α水平降低(P<0.05),血清NO水平升高(P<0.01)。番茄红素干预剂量与血清番茄红素浓度呈二次曲线关系(P<0.01),其中65和85 mg·kg-1组血清番茄红素浓度高于其他各组(P<0.01)。结论番茄红素主要通过影响血液中胆固醇水平以减少Ox-LDL生成,减轻炎性反应,减轻对血管内皮的损伤,维护血脑屏障通透性,间接降低星型胶质细胞活化程度,减少脑P38蛋白磷酸化及IL-1,TNF-α和NO分泌,发挥脑血管和神经元保护作用。

Protective effects of lycopene on cerebral vessels and neurons of hyperlipidemic model rats

OBJECTIVE To study the protective effects of lycopene on cerebral vessels and neurons in hyperlipidemic model rats. METHODS SD rats were fed with hypercholesterolemic diet and ig administered with lycopene 5, 25, 45, 65, 85, 105 and 125 mg·kg-1 simultaneously every day for four weeks. At the same time, normal control group, hyperlipidemic model group and fluvastatin sodium(10 mg·kg-1)group were set up. Total cholesterol(TC), triglycerides(TG), low density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C), oxidized low density lipoprotein(Ox-LDL), total antioxidant capacity(T-AOC), interleukin-1(IL-1), tumor necrosis factor-α(TNF-α), vascular cell adhesion molecule-1(VCAM-1), vascular endothelial growth factor(VEGF) and nitric oxide(NO) levels of the serum and brain were detected by kits. Claudin-5 glial fibrillary acidic protein(GFAP), phosphorylation-P38 protein(p-P38) levels in the brain were detected by Western blotting. Morphological changes of neurons were observed and counted by Nissl staining while lycopene levels were detected by high performance liquid chromatography. RESULTS Compared with the hyperlipidemic model group, serum and cerebral TC, TG, LDL-C, Ox-LDL, IL-1, TNF-α, VCAM-1, VEGF as well as cerebral NO, GFAP, p-P38 levels were decreased in lycopene(25-85 mg·kg-1) groups(P<0.01), but serum T-AOC, NO and cerebral claudin-5 levels as well as the number of neurons were increased(P<0.01). Serum TC, TG, LDL-C, IL-1, TNF-α and cerebral IL-1, TNF-α levels were decreased in lycopene 105 and 125 mg·kg-1 groups(P<0.05), but serum NO levels were increased(P<0.01). The concentration of serum lycopene was quadratic with the dose of lycopene(P<0.01), and the concentrations of lycopene 65 and 85 mg·kg-1 groups were higher than those of other groups(P<0.01). CONCLUSION Lycopene cna reduce Ox-LDL formation mainly by affecting cholesterol levels in the blood, which alleviates the inflammatory response and maintains bloodbrain barrier permeability. Activation in astrocytes is indirectly attenuated, and the production of p-P38 protein, IL-1, TNF-α and NO in the brain is decreased, which reduces hyperlipidemia-induced injury to cerebral vessels and neurons.