目的探讨铅与高脂饮食暴露对大鼠脑皮质的氧化损伤的影响。方法将40只健康成年SPF级雄性SD大鼠随机分为对照组、高脂饮食组、铅暴露组、铅+高脂饮食组,每组10只;其中,对照组、铅暴露组饲喂普通饲料(脂肪≥4%,碳水化化合物≤8%);高脂饮食组及铅+高脂饮食组饲喂高脂饲料(脂肪:45.65%,碳水化合物:37.89%)。对照组及高脂饮食组大鼠自由饮用800 mg/L的乙酸钠溶液,铅暴露组及铅+高脂饮食组大鼠自由饮用800 mg/L的乙酸铅溶液,连续染毒9周。采用Morris水迷宫对大鼠进行学习记忆能力测试;利用电感耦合等离子质谱仪(ICP-MS)测定大鼠脑皮质铅含量;测定血清中甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)的含量以及脑皮质中抑制羟自由基能力、谷胱甘肽-S转移酶(GSH-ST)活力和过氧化氢、微量还原性谷胱甘肽(GSH)、晚期糖基化终末产物(AGEs)的含量。结果与对照组比较,铅暴露组与铅+高脂饮食组大鼠第2天逃避潜伏期延长,高脂饮食组、铅暴露组及铅+高脂饮食组大鼠第3天逃避潜伏期延长,差异均有统计学意义(P<0.05);铅+高脂饮食组大鼠第2、3天逃避潜伏期大于高脂饮食组且差异有统计学意义(P<0.05);此外,与铅暴露组相比,铅+高脂饮食组大鼠逃避潜伏期虽有改变但差异无统计学意义(P>0.05)。铅暴露组与铅+高脂饮食组大鼠皮质中的铅含量均增加,差异有统计学意义(P<0.05);与高脂饮食组比较,铅+高脂饮食组大鼠皮质中的铅含量增加,差异有统计学意义(P<0.05)。铅+高脂饮食组大鼠皮质中的铅含量仅略高于铅暴露组,差异无统计学意义(P>0.05)。与对照组相比,高脂饮食组与铅+高脂饮食组大鼠血清中TG、LDL的含量均增加,HDL的含量降低,差异均有统计学意义(P<0.05);而铅暴露组大鼠血清中TG、LDL、HDL的含量均无明显改变。与铅暴露组相比,铅+高脂饮食组大鼠血清中TG、LDL的含量均增加,HDL的含量降低,差异均有统计学意义(P<0.05)。与对照组比较,高脂饮食组、铅暴露组和铅+高脂饮食组大鼠皮质中AGEs的含量均升高,差异有统计学意义(P<0.05);与铅+高脂饮食组比较,高脂饮食组、铅暴露组大鼠皮质中AGEs的含量均较低,差异有统计学意义(P<0.05)。与高脂饮食组、铅暴露组比较,铅+高脂饮食组大鼠皮质中AGEs的含量增加,差异有统计学意义(P<0.05)。各组大鼠皮质中过氧化氢的含量间比较,差异无统计学意义(P>0.05)。与对照组比较,高脂饮食组、铅暴露组、铅+高脂饮食组大鼠皮质中抑制羟自由基能力、GSH-ST活力、GSH含量均降低,除高脂饮食组抑制羟自由基能力外,差异均有统计学意义(P<0.05)。与铅+高脂饮食组比较,高脂饮食组和铅暴露组大鼠皮质中抑制羟自由基能力和GSH含量均较高,差异有统计学意义(P<0.05),而GSH-ST活力均无明显改变。结论铅和高脂饮食暴露可损伤皮质抗氧化能力,导致氧化损伤的程度加重;铅和高脂饮食联合暴露后大鼠皮质的氧化损伤程度更加严重,提示铅可促进高脂饮食人群的中枢神经系统损伤。 Objective To investigate the effects of lead and high-fat diet on oxidative damage of cerebral cortex in rats. Methods Forty healthy adult Sprague Dawley (SD) male Sprague-Dawley rats were randomly divided into control group, high-fat diet group, lead exposure group and lead + high fat diet group, with 10 rats in each group. In the control group, Diet (fat ≥4%, carbohydrate ≤8%); high-fat diet group and high-fat diet group were fed high fat diet (fat: 45.65%, carbohydrate: 37.89%). The rats in the control group and the high-fat diet group were given 800 mg / L sodium acetate solution freely. The lead exposure group and the lead + high fat diet group were allowed to drink 800 mg / L lead acetate solution for 9 weeks. The Morris water maze was used to test the learning and memory ability of rats. The content of lead in rat cerebral cortex was determined by inductively coupled plasma mass spectrometry (ICP-MS). The content of serum triglyceride (TG), low density lipoprotein (LDL) High density lipoprotein (HDL) and the ability of inhibiting hydroxyl radical in the cerebral cortex, glutathione-S-transferase (GSH-ST) activity and hydrogen peroxide, glutathione (GSH) Glycation end products (AGEs) content. Results Compared with the control group, the escape latency was prolonged on the 2nd day in the lead exposure group and the lead + high fat diet group. The escape latency of the rats in the high fat diet group, the lead exposure group and the lead + high fat diet group was prolonged on the 3rd day, (P <0.05). The escape latency of rats on the first and second days in the lead + high-fat diet group was greater than that in the high-fat diet group (P <0.05). In addition, The escaping latency of the rats in the ratio of + Pb + high fat diet group was not significantly different (P> 0.05). The levels of lead in cortex of lead exposure group and lead + high-fat diet group all increased, the difference was statistically significant (P <0.05). Compared with high fat diet group, lead Content increased, the difference was statistically significant (P <0.05). Lead content in the cortex of lead + high-fat diet group was only slightly higher than that of lead exposure group, with no significant difference (P> 0.05). Compared with the control group, the content of TG and LDL in the serum of the high-fat diet group and the lead + high-fat diet group increased, the content of HDL decreased, the difference was statistically significant (P <0.05); while the lead exposure group Serum TG, LDL, HDL levels were not significantly changed. Compared with the lead exposed group, the content of TG and LDL in the serum of the rats in the lead + high fat diet group increased and the content of HDL decreased, with statistical significance (P <0.05). Compared with the control group, the content of AGEs in the cortex of the high-fat diet group, the lead exposure group and the lead + high-fat diet group were significantly increased (P <0.05), compared with the lead + high fat diet group , High-fat diet group, lead exposure group rats cortical AGEs content were lower, the difference was statistically significant (P <0.05). Compared with the high fat diet group and the lead exposure group, the content of AGEs in the cortex of the lead + high fat diet group increased significantly, with significant difference (P <0.05). There was no significant difference in the content of hydrogen peroxide between cortex of rats in each group (P> 0.05). Compared with the control group, the ability of hydroxyl radical inhibition, GSH-ST activity and GSH content in the cortex of high-fat diet group, lead exposure group and lead + high fat diet group were decreased, except the high fat diet group inhibited the hydroxyl radical capacity The differences were statistically significant (P <0.05). Compared with the lead + high-fat diet group, the high-fat diet group and the lead exposure group had a higher level of inhibition of hydroxyl radical and GSH content in the cortex (P <0.05), while GSH-ST activity No significant change. Conclusion Exposure of lead and high-fat diet can damage the cortical antioxidant capacity, leading to the increased degree of oxidative damage. The oxidative damage of cortex in rats exposed to lead and high-fat diet is more serious, suggesting that lead may promote central nervous system System damage.