白藜芦醇对高脂饮食去卵巢肥胖大鼠海马组织脑源性神经营养因子水平的影响

 目的：探讨去卵巢联合高脂饮食诱导的肥胖大鼠海马组织中脑源性神经营养因子（BDNF）、雌激素受体α (ERα)和雌激素受体β (ERβ) 表达的变化，同时观察白藜芦醇对这些改变的影响。方法：50只3月龄雌性Wistar大鼠随机分为5组：假手术普通饮食对照（C）组、假手术高脂饮食（H）组、单纯去卵巢（O）组、去卵巢高脂饮食（O+H）组和白藜芦醇（40 mg·kg-1·d-1）+去卵巢高脂饮食(O+H+R)组。3月后抽取股动脉血检测血清雌二醇（E2）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇(LDL-C)含量；实时荧光定量PCR法检测海马BDNF、ERα和ERβ mRNA表达，蛋白免疫印迹法及ELISA法分别检测海马BDNF蛋白含量。结果：与C组比较，H组大鼠血清TC和LDL-C含量升高，海马BDNF水平显著降低（P<0.05或P<0.01），O组大鼠血清E2水平降低，TC含量升高，海马BDNF 水平及ERα、ERβ mRNA表达均明显下降（P<0.05或P<0.01）；O+H组大鼠血清TC含量升高，HDL-C水平降低，海马BDNF 水平降低，与C组、H组和O组比较均有显著差异（P<0.05或P<0.01），海马ERα和ERβ mRNA表达下降，与C组和H组比较差异显著（P<0.05或P<0.01）；O+H+R组大鼠血清E2水平升高，TC含量降低，海马ERα和ERβ mRNA表达水平及BDNF含量均明显增加，与O+H组比较有显著差异（P<0.05或P<0.01）。结论：去卵巢联合高脂饮食显著降低大鼠海马ERα和ERβ mRNA表达及BDNF水平，而白藜芦醇能够明显改善绝经后肥胖大鼠的血脂水平，上调海马ERα和ERβ mRNA表达，增加海马BDNF水平。

Effect of resveratrol on level of brain-derived neurotrophic factor in hippocampus of obese rats induced by ovariectomy and high-fat diet

AIM：To explore the effects of resveratrol on the level of brain-derived neurotrophic factor (BDNF) and  the mRNA expression of estrogen receptor α (ERα) and estrogen receptor β (ERβ) in hippocampus of obese rats induced by ovariectomy and high-fat diet. METHODS：Fifty female Wistar rats, aged 3 months, were randomly divided into 5 groups: control (C) group, sham operation plus high-fat diet (H) group, ovariectomy plus normal diet (O) group, ovariectomy plus high-fat diet (O+H) group, and ovariectomy plus high-fat diet and treated with resveratrol (40  mg·kg-1·d-1) (O+H+R) group. Three months later, the blood was collected from the femoral artery to detect the serum concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and estradiol (E2). The mRNA expression of ERα, ERβ and BDNF in the hippocampus was determined by real-time PCR. The protein level of BDNF in hippocampal tissues was detected by ELISA and Western blotting. RESULTS：Compared with C group, the serum levels of TC and LDL-C in H group were increased, and the hippocampal level of BDNF was decreased. The rats in O group had higher concentration of serum TC, and lower levels of serum E2 and the mRNA expression of ERα, ERβ and BDNF in the hippocampus than those in C group. Compared with C,H and O groups, the level of serum TC was higher, and the level of serum E2 and the expression of BDNF in the hippocampus was lower in O+H group. The mRNA expression of ERα  and ERβ in hippocampus was also reduced as compared with C group and H group. After treated with resveratrol, the rats in O+H+R group showed lower level of serum TC, and higher levels of serum E2, hippocampal BDNF and mRNA expression of ERα and ERβ than those in O+H group. CONCLUSION：Ovariectomy combined with high-fat diet decreases the mRNA expression of ERαand ERβ and the level of BDNF in the rat hippocampus. Resveratrol improves the blood lipid metabolism and up-regulates the mRNA expression of ERα/ERβ and the level of BDNF in the hippocampus in obese rats induced by ovariectomy and high-fat diet.