短链脂肪酸对新生幼鼠肝脑发育及免疫功能的影响

doi:10.11843/j.issn.0366-6964.2025.11.019

畜牧兽医学报 ›› 2025, Vol. 56 ›› Issue (11): 5588-5599.doi: 10.11843/j.issn.0366-6964.2025.11.019

短链脂肪酸对新生幼鼠肝脑发育及免疫功能的影响

李新科¹^,²^,³(), 杨雪²^,³, 张萱²^,³, 孟璐²^,³, 张养东²^,³, 王加启²^,³, 郑楠²^,³^,*()

1. 青岛农业大学食品科学与工程学院, 青岛 266109
2. 中国农业科学院北京畜牧兽医研究所农业农村部奶及奶制品质量安全控制重点实验室, 北京 100193
3. 中国农业科学院北京畜牧兽医研究所农业农村部奶产品质量安全风险评估实验室(北京), 北京 100193

收稿日期:2024-11-08 出版日期:2025-11-23 发布日期:2025-11-27
通讯作者: 郑楠 E-mail:lixinke6233@163.com;zhengnan@caas.cn
作者简介:李新科(2000-)，男，湖南衡山人，硕士生，主要从事奶产品质量安全风险评估和营养功能评价研究，E-mail: lixinke6233@163.com
基金资助:
国家重点研发计划(2022YFD1301005)；国家重点研发计划(2022YFD1301004)；中国农业科学院科技创新工程(ASTIP-IAS12)

Effects of Short-Chain Fatty Acids on Liver and Brain Development and Immune Function in Neonatal Mice

LI Xinke¹^,²^,³(), YANG Xue²^,³, ZHANG Xuan²^,³, MENG Lu²^,³, ZHANG Yangdong²^,³, WANG Jiaqi²^,³, ZHENG Nan²^,³^,*()

1. College of Food Science and Engineering, Qingdao Agricultural University, Qingdao 266109, China
2. Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China
3. Laboratory of Quality and Safety Risk Assessment for Dairy Products of Ministry of Agriculture and Rural Affairs(Beijing), Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, China

Received:2024-11-08 Online:2025-11-23 Published:2025-11-27
Contact: ZHENG Nan E-mail:lixinke6233@163.com;zhengnan@caas.cn

摘要/Abstract

摘要：

旨在探讨不同短链脂肪酸对新生幼鼠生长发育、行为活动以及脑部和肝微观结构与炎症因子表达的影响。试验选取刚出生的C57BL/6J幼鼠56只(共7组，每组8只)，每个组别的幼鼠均来自于八窝不同的母鼠，连续28 d进行不同SCFAs浓度的灌胃处理。处理组包括：CTL(0.9%生理盐水)、SF-900组(900 mg·kg^-1 BW甲酸钠)、SF-1400组(1 400 mg·kg^-1 BW甲酸钠)、SP-2(20 mg·kg^-1 BW丙酸钠)、SP-200(200 mg·kg^-1 BW丙酸钠)、SV-5(5 mg·kg^-1 BW戊酸钠)和SV-20(20 mg·kg^-1 BW戊酸钠)。记录幼鼠的体重变化、脑指数和肝脏指数，并通过旷场试验评估其自发性活动。同时，检测脑组织和肝组织中相关基因的表达水平。结果表明，丙酸(SP-2)和戊酸(SV-5)显著促进幼鼠的体重增长，丙酸处理组(SP-2)体重增加最为显著，增长率达到12.83%。HE染色结果显示，各组幼鼠组织器官(脑、肝)微观结构均保持完整，未见显著组织学病理改变。行为学试验表明，甲酸处理组(SF-1400)和戊酸处理组(SV-5，SV-20)幼鼠表现出显著增强的自主活动性和探索行为，提示这些SCFAs可能通过中枢神经系统调节行为反应。此外，戊酸处理组(SV-5，SV-20)调节了脑组织中BDNF和TRKB等神经因子的表达，可能通过增强神经生长因子水平及其受体信号通路(如GPR41)促进神经元生存和突触可塑性。RT-qPCR检测结果揭示，丙酸处理显著上调了肝组织中抗炎因子IL-4和IL-10的表达，并下调了促炎因子IL-6、TNF-α和IFN-γ的表达，这表明丙酸对肝的免疫功能具有积极调节作用。综上所述，SCFAs特别是丙酸和戊酸，在调控免疫反应和神经发育相关通路方面，对新生幼鼠的生长发育和行为表现产生了积极影响。这些结果支持了SCFAs在改善免疫功能和促进神经发育中的潜在作用。

关键词: 短链脂肪酸, 生长发育, 炎症因子, 行为学试验, 微观结构

Abstract:

This study aims to investigate the effects of different short-chain fatty acids (SCFAs) on the growth, behavior, microstructure of brain and liver, and the expression of inflammatory cytokines in young mice. The experimental subjects were newborn C57BL/6J pups (7 groups, 8 mice in each group). The pups in each group were from eight litters of different female mice, and were given gavage with different SCFAs concentrations for 28 consecutive days. The treatment groups were: CTL (0.9% saline), SF-900 group (900 mg·kg^-1 BW sodium formate), SF-1400 group (1 400 mg·kg^-1 BW sodium formate), SP-2 (20 mg·kg^-1 BW sodium propionate), SP-200 (200 mg·kg^-1 BW sodium propionate), SV-5 (5 mg·kg^-1 BW sodium valerate), and SV-20 (20 mg·kg^-1 BW sodium valerate). Body weight, brain index, and liver index were recorded, and spontaneous activity was assessed using the open-field test. Additionally, the expression levels of relevant genes in brain and liver tissues were measured. The results indicated that propionate (SP-2) and valerate (SV-5) significantly enhanced weight gain in young mice, with the propionate group (SP-2) showing the most significant weight increase by 12.83%. HE staining revealed that the microstructure of brain and liver tissues remained intact across all groups, with no significant pathological changes. Behavioral tests showed that formate-treated mice (SF-1400) and valerate-treated mice (SV-5, SV-20) exhibited significantly increased spontaneous activity and exploratory behavior, suggesting that these SCFAs might modulate behavioral responses through the central nervous system. Furthermore, the valerate-treated groups (SV-5, SV-20) regulated the expression of neurotrophic factors BDNF and TRKB in the brain, potentially promoting neuronal survival and synaptic plasticity through increased levels of neurotrophic factors and receptor signaling pathways (such as GPR41). RT-qPCR results revealed that propionate treatment significantly upregulated the expression of anti-inflammatory cytokines IL-4 and IL-10 in liver tissues, while downregulating pro-inflammatory cytokines IL-6, TNF-α, and IFN-γ, indicating that propionate has a positive regulatory effect on liver immune function. In conclusion, SCFAs, particularly propionate and valerate, positively influence the growth and behavior of young mice by regulating immune responses and neurodevelopmental pathways. These findings support the potential role of SCFAs in improving immune function and promoting neurodevelopment.

Key words: short-chain fatty acids, growth and development, inflammatory cytokines, behavioral testing, microstructure

中图分类号:

TS201.4

李新科, 杨雪, 张萱, 孟璐, 张养东, 王加启, 郑楠. 短链脂肪酸对新生幼鼠肝脑发育及免疫功能的影响[J]. 畜牧兽医学报, 2025, 56(11): 5588-5599.

LI Xinke, YANG Xue, ZHANG Xuan, MENG Lu, ZHANG Yangdong, WANG Jiaqi, ZHENG Nan. Effects of Short-Chain Fatty Acids on Liver and Brain Development and Immune Function in Neonatal Mice[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(11): 5588-5599.

图/表 6

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基因名称 Gene name	参考序列登录号 Reference GenBank ID	引物序列(5′→3′) Primer sequences(5′→3′)	产物长度/bp Product length
GAPDH	NM_008084	F: AGGTCGGTGTGAACGGATTTG R: TGTAGACCATGTAGTTGAGGTCA	123
BDNF	NM_001048141	F: CTCCGGGTTGGTATACTGGG R: TCTCACCTGGTGGAACTTCTTT	104
MAP2	NM_008632	F: GCCAGCCTCAGAACAAACAG R: AAGGTCTTGGGAGGGAAGAAC	146
TRKB	NM_001025074	F: AAGCCGCGCGGACAG R: ACCTCAGGGCTGGGGAG	74
GPR41	NM_001033316	F: TGTCCAATACTCTGCATCTGTG R: CACGAGGAACACCAACAGGTA	94
GPR43	NM_146187	F: AGACAGAAAAGGAGCTGACAGG R: TCTGGGGTCATTCTCCTTGG	97
IL-4	NM_021283	F: CTCACAGCAACGAAGAACACC R: CTGCAGCTCCATGAGAACACT	132
IL-10	NM_010548	F: GGCCCAGAAATCAAGGAGCA R: GAGAAATCGATGACAGCGCC	87
IL-6	NM_031168	F: GACAAAGCCAGAGTCCTTCAGA R: TGTGACTCCAGCTTATCTCTTGG	76
TNF-α	NM_013693	F: GATCGGTCCCCAAAGGGATG R: CCACTTGGTGGTTTGTGAGTG	92
IFN-γ	NM_008337	F: GGAGGAACTGGCAAAAGGATG R: GTTGCTGATGGCCTGATTGT	107

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短链脂肪酸对新生幼鼠肝脑发育及免疫功能的影响

Effects of Short-Chain Fatty Acids on Liver and Brain Development and Immune Function in Neonatal Mice

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