Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Affiliated Hospital of Shaanxi University of Chinese Medicine, Shaanxi University of Chinese Medicine, Xianyang 712000, China.
Ecotoxicol Environ Saf. 2024 Sep 15;283:116832. doi: 10.1016/j.ecoenv.2024.116832. Epub 2024 Aug 12.
Heat stress (HS) disrupts intestinal microbiota, glycolipid metabolism, and hepatic mitochondrial function in late gestational mice. Baicalin (BAI), a Chinese herbal medicine known for its heat-clearing and anti-inflammatory properties, has shown promise in modulating intestinal microecology and mitigating inflammation in various organs. This study investigates whether baicalin attenuates HS-induced intestinal microbial dysbiosis and liver damage in pregnant mice during late gestation. Twenty-four pregnant mice were randomly assigned to four groups, including thermoneutral (TN) (24 ± 1 ℃), HS (35 ± 1 ℃), HS+BAI200 (oral gavaged with 200 mg/kg BW of BAI), and HS+BAI400 (oral gavaged with 400 mg/kg BW of BAI). 400 mg/kg BAI treatment markedly decreased the rectal temperature and increased fetal weight in HS pregnant mice. Furthermore, 400 mg/kg BAI administration effectively ameliorated HS-induced hepatic damage and lipid disorders, reducing HSP70, AST, and ALT levels while increasing TG concentration. Notably, it activated a network of genes involved in lipid synthesis, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and oxidation, such as peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmityl transferase 1 beta (CPT1β). Moreover, BAI intervention restored the intestinal morphology and barrier function, evidenced by increased intestinal villus height, the ratio of villus height to crypt depth, and colonic goblet cells numbers. 400 mg/kg of BAI treatment up-regulated the expression of tight junction proteins, such as claudin-1 and Zonula Occludens-1 (ZO-1), in the jejunum and ileum, counteracting HS-induced downregulation. High-throughput sequencing showed that BAI treatment altered cecal microbial composition, increasing the relative abundance of beneficial Bacteroidota and decreasing Deferribacterota, Turicibacter, and Akkermansia. Spearman's correlation analysis highlighted significant correlations between differential cecal microbiota and physiological indexes. In conclusion, BAI administration alleviated adverse impacts in heat-exposed mice during late gestation, improving maternal physiological parameters, and ameliorating hepatic damage with altered cecal microbial composition. The findings suggest that BAI may regulate the gut-liver axis by modulating intestinal morphology, microecology, and hepatic function.
热应激（HS）破坏妊娠晚期小鼠的肠道微生物群、糖脂代谢和肝线粒体功能。黄芩苷（BAI）是一种具有清热抗炎作用的中草药，已被证明在调节肠道微生态和减轻各种器官炎症方面具有潜力。本研究旨在探讨黄芩苷是否能减轻妊娠晚期 HS 引起的孕鼠肠道微生物失调和肝损伤。将 24 只孕鼠随机分为 4 组，包括常温（TN）（24±1℃）、HS（35±1℃）、HS+BAI200（口服给予 200mg/kg BW 的 BAI）和 HS+BAI400（口服给予 400mg/kg BW 的 BAI）。400mg/kg BAI 处理显著降低了 HS 孕鼠的直肠温度并增加了胎儿体重。此外，400mg/kg BAI 给药可有效改善 HS 引起的肝损伤和脂质紊乱，降低 HSP70、AST 和 ALT 水平，同时增加 TG 浓度。值得注意的是，它激活了一个涉及脂质合成的基因网络，包括脂肪酸合酶（FAS）、乙酰辅酶 A 羧化酶（ACC）和氧化，如过氧化物酶体增殖物激活受体 alpha（PPARα）、肉碱棕榈酰转移酶 1β（CPT1β）。此外，BAI 干预恢复了肠道形态和屏障功能，表现为增加了空肠绒毛高度、绒毛高度与隐窝深度的比值和结肠杯状细胞数量。400mg/kg BAI 处理上调了空肠和回肠中紧密连接蛋白的表达，如 Claudin-1 和 Zonula Occludens-1（ZO-1），逆转了 HS 诱导的下调。高通量测序显示，BAI 处理改变了盲肠微生物组成，增加了有益的拟杆菌门和减少了脱硫弧菌科、Turicibacter 科和 Akkermansia 属的相对丰度。Spearman 相关分析突出了差异盲肠微生物与生理指标之间的显著相关性。总之，BAI 给药缓解了妊娠晚期热暴露小鼠的不良影响，改善了母体生理参数，并通过改变盲肠微生物组成改善了肝损伤。研究结果表明，BAI 可能通过调节肠道形态、微生态和肝功能来调节肠-肝轴。
