唾液酸干预对孤独症模型大鼠肠道功能的影响
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1.齐齐哈尔市中医医院;2.齐齐哈尔医学院

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国家自然科学基金项目(No.82103869);黑龙江省省属本科高校基本科研业务费项目(No.2024-KYYWF-0364)


EFFECTS OF SIALIC ACID INTERVENTION ON INTESTINAL FUNCTION IN AUTISM MODEL RATS
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1.Qiqihar Traditional Chinese Medicine Hospital;2.Qiqihar Medical University

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    摘要:

    【摘要】 目的 探讨孕乳期的唾液酸(sialic acid, SA)干预对孤独症模型鼠肠道功能的影响。方法 SPF级Wistar雌性及雄性成年大鼠各30只进行交配,成功受孕的大鼠被随机分配到丙戊酸(valproate, VPA)诱导的模型组(VPA组)、唾液酸高剂量组(SAH组)、(唾液酸中剂量组)SAM组、唾液酸低剂量(SAL组)及对照组(CON组)(每组n=6)单笼单只饲养。在孕12.5天,VPA组和SA干预各组的孕鼠分别接受单次腹腔注射600 mg/kg的丙戊酸钠(VPA),而CON组孕鼠则给予等量的生理盐水。SA干预时间从E12.5天到子代出生后第21天。随后,采集各组仔代大鼠粪便,通过16S rRNA测序检测肠道菌群的多样性及结构,采用胭脂红灌胃检测各组大鼠的肠道转运速度,应用ELISA方法检测各组大鼠肠道相关神经递质(P物质、脑啡肽、5-羟色胺、血管活性肠肽、谷氨酸、γ-氨基丁酸)的表达水平。结果 高剂量SA干预并未影响VPA诱导的孤独症模型鼠的肠道菌群多样性,但改变了肠道菌群的结构,提高了普雷沃氏菌_NK3B31群、普雷沃菌、普氏菌、拟普雷沃菌、毛螺菌、拟杆菌等的丰度水平(P<0.05);提高了模型大鼠肠道转运速度;促进了模型鼠5-羟色胺、血管活性肠肽及γ-氨基丁酸的表达水平。结论 孕乳期的SA干预影响了VPA诱导的孤独症模型鼠肠道转运速度,改变了肠道菌群结构,提高了血管活性肠肽、5羟色胺及γ-氨基丁酸的表达水平。

    Abstract:

    【Abstract】 Objective To explore the effects of sialic acid intervention during pregnancy and lactational period on the intestinal function of autism model rats. Methods Thirty SPF-grade adult male and female Wistar rats were mated. The successfully pregnant rats were randomly assigned to valproate induced model group (VPA group), high dose sialic acid group (SAH group), medium dose sialic acid group (SAM group), low dose sialic acid group (SAL group) and control group (CON group) (n=6 per group) and were housed individually in single cages. On the 12.5th day of pregnancy, the pregnant rats in the VPA group and the SA intervention groups were given a single intraperitoneal injection of 600 mg/kg of sodium valproate (VPA), while the pregnant rats in the CON group were given an equal amount of normal saline. The SA intervention period was from E12.5 to the 21st day after the offspring born. Subsequently, the feces of the offspring rats in each group were collected. The diversity and structure of the gut microbiota were detected by 16S rRNA sequencing. The intestinal transit speed of the rats in each group was detected by intragastric administration of carmine. The expression levels of intestinal-related neurotransmitters (substance P, enkephalin, 5-hydroxytryptamine, vasoactive intestinal peptide, glutamate, gamma-aminobutyric acid) in the blood of the rats in each group were detected by the ELISA method. Results High-dose SA intervention did not affect the diversity of the gut microbiota in the VPA-induced autism model rats, but it changed the structure of the gut microbiota and increased the abundance levels of Prevotella_NK3B31 group, Prevotella, Prevotella spp., Alloprevotella, Lachnospira, Ruminococcus, Bacteroides, etc. (p < 0.05). It promoted the intestinal transit speed of the model rats. Moreover, it increased the levels of vasoactive intestinal peptide, 5-hydroxytryptamine, and gamma-aminobutyric acid in the serum of the rats. Conclusion SA intervention during pregnancy and lactational period affects the intestinal transit speed of VPA-induced autism model rats, changes the structure of the gut microbiome, and increases the expression levels of vasoactive intestinal peptide, 5-hydroxytryptamine, and gamma-aminobutyric acid.

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  • 收稿日期:2025-04-21
  • 最后修改日期:2025-07-21
  • 录用日期:2025-09-24
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