植物乳杆菌通过调控胆汁酸代谢并抑制海马体NLRP3蛋白表达缓解铅暴露导致的小鼠学习记忆障碍

doi:10.12122/j.issn.1673-4254.2026.02.04

摘要/Abstract

摘要：

目的探讨植物乳杆菌（L.plantarum）缓解铅暴露引起的学习记忆障碍的作用及机制。方法将24只C57BL/6J小鼠随机分为对照组、铅组和L.plantarum+铅组（8只/组），对照组的小鼠只喝无菌蒸馏水。铅组、L.plantarum+铅组小鼠饮用溶于无菌蒸馏水的氯化铅溶液，对照组、铅组小鼠每天灌胃0.1 mL磷酸盐缓冲盐水1次，L.plantarum+铅组小鼠每天灌胃含有L.plantarum的磷酸盐缓冲盐水0.1 mL1次，其中铅的暴露剂量为100 mg/L，通过灌胃进行L.plantarum（10⁹CFU）干预。干预10周后，采用Morris水迷宫实验评价小鼠的学习记忆能力，电感耦合等离子体-质谱法（ICP-MS）检测小鼠血铅含量，液相色谱-质谱联用（LC-MS）检测小鼠血清胆汁酸含量，HE染色检测海马组织病理学改变，免疫组化法观察海马区小胶质细胞形态学改变及活化状态，ELISA实验检测小鼠血清炎性细胞因子TNF-α和IL-1β含量，Western blotting实验检测NLRP3和TGR5蛋白表达水平。结果与单独铅暴露组相比，L.plantarum干预增加了小鼠在Morris水迷宫实验中目标象限中的探索时间（P<0.05）、游泳距离（P<0.05）和平台穿越次数（P<0.05），减少了寻找水下隐藏平台的潜伏期（P<0.05）；并且L.plantarum干预部分逆转铅暴露引起的血清中脱氧胆酸（P<0.05）、3-羟基脱氧胆酸和3-羟基熊去氧胆酸（P<0.05）、3-硫代脱氧胆酸（P<0.01）和3-硫代α-甲基胆酸（P<0.05）等胆汁酸含量的下降；同时L.plantarum干预恢复了铅暴露诱导的海马体病理改变，降低铅暴露所致的小鼠神经炎症因子IL-1β、TNF-α和海马体NLRP3蛋白水平。结论 L.plantarum可缓解铅暴露引起的学习记忆障碍，其机制可能与胆汁酸代谢以及抑制NLRP3蛋白有关。

关键词: 铅暴露, 学习记忆, 植物乳杆菌, 靶向代谢组学, NLRP3

Abstract:

Objective To explore the mechanism of Lactobacillus plantarum (L. plantarum) for alleviating learning and memory impairments caused by lead exposure. Methods Twenty-four C57BL/6J mice were randomized equally into control group, lead exposure (100 mg/L) group, and L.plantarum treatment group with daily gavage of L.plantarum (10⁹ CFU) for 10 weeks. Learning and memory abilities of the mice were evaluated using Morris water maze test, and blood lead level and bile acid levels were determined using inductively coupled plasma mass spectrometry (ICP-MS) and liquid chromatography-mass spectrometry (LC-MS), respectively. Hippocampal pathologies of the mice were examined with HE staining, and immunohistochemistry was used to observe morphological changes and microglia activation in the hippocampus. Serum levels of TNF‑α and IL-1β of the mice were determined with ELISA, and hippocampal expression levels of NLRP3 and TGR5 proteins were detected using Western blotting. Results Compared with those in lead exposure group, the mice receiving L.plantarum intervention showed significantly increased exploration time, swimming distance, and target platform crossings with reduced latency period to find the hidden platforms in Morris water maze test. L.plantarum intervention partially reversed lead exposure induced reduction of serum levels of deoxycholic acid, 3-hydroxydeoxycholic acid, 3-hydroxyursodeoxycholic acid, 3-thiodeoxycholic acid, and 3-thio‑α‑methylcholic acid. The treatment also significantly reduced hippocampus pathologies in mice with lead exposure, and reduced their serum levels of IL-1β and TNF‑α and hippocampal NLRP3 protein expression levels. Conclusion L.plantarum can alleviate learning and memory impairments caused by lead exposure in mice possibly by regulating bile acid metabolism and inhibiting hippocampal expression of NLRP3 protein.

Key words: lead exposure, learning and memory, Lactobacillus plantarum, targeted metabolomics, NLRP3

李立凡, 余伟健, 谭美涛, 李韵婷, 刘安飞, 孟晓静. 植物乳杆菌通过调控胆汁酸代谢并抑制海马体NLRP3蛋白表达缓解铅暴露导致的小鼠学习记忆障碍[J]. 南方医科大学学报, 2026, 46(2): 271-277.

Lifan LI, Weijian YU, Meitao TAN, Yunting LI, Anfei LIU, Xiaojing MENG. Lactobacillus plantarum alleviates lead exposure-induced learning and memory impairment in mice by regulating bile acid metabolism and inhibiting hippocampal NLRP3 expression[J]. Journal of Southern Medical University, 2026, 46(2): 271-277.

图/表 4

图1 L.plantarum干预缓解铅诱导的学习记忆障碍

Fig.1 L.plantarum supplementation alleviates lead-induced learning and memory impairments in mice as shown by performance in Morris water maze test. A: Swimming speed. B: Escape latency on day 4. C: Percentage of swimming distance in the target quadrant. D: Percentage of swimming time in the target quadrant. E: Number of crossings over the target platform. n=8, *P<0.05, ***P<0.001, ****P<0.0001.

图2 ICP-MS 检测小鼠血铅浓度

Fig.2 ICP-MS detection of blood lead concentration in mice (n=6). ****P<0.0001.

图3 补充L.plantarum可以部分恢复铅诱导胆汁酸代谢失调

Fig.3 L.plantarum treatment partially restores lead-induced disorders in bile acid metabolism. A: Principal component analysis of serum bile acid targeted metabolic profiles in different groups. B: Quantitative comparison of serum bile acid levels among the 3 groups. *P<0.05, **P<0.01, ***P<0.001.

图4 L.plantarum通过抑制NLRP3炎症小体缓解铅诱导的神经炎症

Fig.4 L.plantarum supplementation alleviates lead-induced neuroinflammation by inhibiting NLRP3 inflammasome. A: HE staining and immunohistochemistry for IBA1 expression in the hippocampal DG region. The red arrow in the upper panel indicates hippocampal pathology, and the arrows in the lower panel indicate activated microglia. B: Levels of IL-1β and TNF-α in the hippocampal tissue and serum of the mice detected using ELISA (n=5). C: Western blotting for detecting TGR5 and NLRP3 expression levels in the hippocampus (n=3). *P<0.05, **P<0.01, ***P<0.001.

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