Department of Neurology, Zhuji Affiliated Hospital of Shaoxing University, Zhuji, Zhejiang, China.
College of Forensic Medicine, Shanxi Medical University, Taiyuan City, Shanxi Province, China.
World Neurosurg. 2020 Jun;138:758-763. doi: 10.1016/j.wneu.2020.01.165. Epub 2020 Jan 29.
We sought to investigate the effects and mechanism of lead and a high-fat diet on cognitive function and the central nervous system in mice.
Eighty-four healthy male mice were randomly divided into a control group (n = 21) (fed with common diet and free drinking), a lead exposure group (n = 21) (fed with common diet and 300 mg/L lead acetate solution), a high-fat group (n = 21) (fed with high-fat diet and free drinking), and a lead + high-fat group (n = 21) (fed with high-fat diet and 300 mg/L lead acetate solution). In 10 weeks after lead exposure, the mice of all groups were tested for the cognition, learning and memory abilities, body weight, serum triglyceride (TG), low-density lipoprotein, and high-density lipoprotein, as well as for the contents of lead, interleukin 6 (IL-6), interleukin 17 (IL-17), interferon γ, advanced glycation end products (AGEs), glutathione S-transferase (GSH-ST), and hydrogen peroxide in the brain tissues.
Compared with the control group and the lead-exposed group, the body weights of mice in the high-fat group and the lead + high-fat group increased significantly from the sixth week of the experiment, of which the difference was statistically significant (P < 0.05). Compared with the control group and the high-fat group, the lead content in brain tissue of the lead exposure group and the lead + high-fat group increased significantly, of which the difference was statistically significant (P < 0.05). Compared with the control group, the escape latent period, triglyceride, low-density lipoprotein, IL-6, IL-17, interferon γ, and AGEs of the remaining 3 groups increased significantly, but the recognition index, passing platform times, high-density lipoprotein, and GSH-ST significantly decreased (P < 0.05); the second and third escape latent periods, IL-6, IL-17, and AGEs of lead + high-fat group, were obviously higher than the remaining 3 groups, but the passing platform times were obviously lower than the remaining 3 groups, of which the difference was statistically significant. The content of hydrogen peroxide in brain tissues had no difference among groups (P > 0.05).
The lead and high-fat diet resulted in lipid metabolism disorders and impaired the cognitive function and central nervous system by promoting the secretion of inflammatory factors in glial cells, inducing the inflammatory reaction of brain tissue, inhibiting GSH-ST expression, and increasing AGEs content.
本研究旨在探讨铅和高脂饮食对小鼠认知功能和中枢神经系统的影响及作用机制。
将 84 只健康雄性小鼠随机分为对照组（n=21）（普通饮食+自由饮水）、铅暴露组（n=21）（普通饮食+300mg/L 醋酸铅溶液）、高脂组（n=21）（高脂饮食+自由饮水）和铅+高脂组（n=21）（高脂饮食+300mg/L 醋酸铅溶液）。在铅暴露 10 周后，检测各组小鼠的认知、学习和记忆能力、体重、血清甘油三酯（TG）、低密度脂蛋白和高密度脂蛋白，以及脑组织中铅、白细胞介素 6（IL-6）、白细胞介素 17（IL-17）、干扰素γ、晚期糖基化终产物（AGEs）、谷胱甘肽 S-转移酶（GSH-ST）和过氧化氢的含量。
与对照组和铅暴露组相比，高脂组和铅+高脂组小鼠从实验第 6 周开始体重明显增加，差异有统计学意义（P<0.05）。与对照组和高脂组相比，铅暴露组和铅+高脂组脑组织中的铅含量明显增加，差异有统计学意义（P<0.05）。与对照组相比，其余 3 组的逃避潜伏期、甘油三酯、低密度脂蛋白、IL-6、IL-17、干扰素γ和 AGEs 明显升高，而识别指数、通过平台次数、高密度脂蛋白和 GSH-ST 明显降低（P<0.05）；铅+高脂组的第 2 和第 3 次逃避潜伏期、IL-6、IL-17 和 AGEs 明显高于其余 3 组，而通过平台次数明显低于其余 3 组，差异有统计学意义。各组脑组织中过氧化氢的含量差异无统计学意义（P>0.05）。
铅和高脂饮食通过促进胶质细胞炎症因子的分泌，诱导脑组织炎症反应，抑制 GSH-ST 表达，增加 AGEs 含量，导致脂质代谢紊乱，损害认知功能和中枢神经系统。
