桃红四物汤对缺血性中风模型小鼠肠道菌群紊乱所致炎症损伤的保护作用。
Protective effect of Tao Hong Si Wu Decoction against inflammatory injury caused by intestinal flora disorders in an ischemic stroke mouse model.
机构信息
Department of Pharmacy, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, 230031, China.
School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China.
出版信息
BMC Complement Med Ther. 2024 Mar 18;24(1):124. doi: 10.1186/s12906-024-04417-1.
BACKGROUND AND AIMS
Recent studies have shown that intestinal flora are involved in the pathological process of ischemic stroke (IS). The potential protective effect of the traditional Chinese prescription, Tao Hong Si Wu Decoction (THSWD), against inflammatory injury after IS and its underlying mechanisms of action were investigated in the current study.
METHODS
Fifty SPF(Specefic pathogen Free) male C57 mice were randomly assigned to sham operation, model, THSWD low-dose (6.5 g/kg), medium-dose (13 g/kg) and high-dose (26 g/kg) groups (10 mice per group). Mouse models of transient middle cerebral artery occlusion were prepared via thread embolism. Neurological function score, hematoxylin-eosin (HE) staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), 16S ribosomal DNA (rDNA) sequencing, quantitative reverse transcription PCR (qRT-PCR) and other methods were employed to elucidate the underlying molecular mechanisms.
RESULTS
Notably, THSWD induced a reduction in the neurological function score (P < 0.01) and neuronal injury in brain tissue, increase in protein expression of Claudin-5 and zonula occludens-1 (ZO-1) in brain tissue(P < 0.01), and decrease in serum lipopolysaccharide (LPS)(P < 0.01), diamine oxidase (DAO)(P < 0.01) and D-lactic acid(P < 0.01, P < 0.05) levels to a significant extent. THSWD also inhibited the levels of tumor necrosis factor-α (TNF-α)(P < 0.01) and interleukin - 1β (IL-1β)(P < 0.01) in brain tissue, and increased alpha and beta diversity in ischemic stroke mice, along with a certain reversal effect on different microflora. Finally, THSWD inhibited the polarization of microglia cells(P < 0.01) and decreased the protein and gene expression of toll-like receptor-4 (TLR-4)(P < 0.01, P < 0.05) and nuclear factor kappa B (NF-κB)(P < 0.01) in brain tissue.
CONCLUSION
Our data indicate that THSWD may interfere with inflammatory response in ischemic stroke by regulating intestinal flora and promoting intestinal barrier repair.
背景与目的
最近的研究表明，肠道菌群参与了缺血性中风（IS）的病理过程。本研究旨在探讨传统中药桃红四物汤（THSWD）对 IS 后炎症损伤的潜在保护作用及其作用机制。
方法
将 50 只 SPF（无特定病原体）雄性 C57 小鼠随机分为假手术组、模型组、THSWD 低剂量（6.5 g/kg）、中剂量（13 g/kg）和高剂量（26 g/kg）组（每组 10 只）。采用线栓法制备短暂性大脑中动脉闭塞模型。采用神经功能评分、苏木精-伊红（HE）染色、免疫组织化学、酶联免疫吸附试验（ELISA）、16S 核糖体 DNA（rDNA）测序、定量逆转录 PCR（qRT-PCR）等方法阐明其潜在的分子机制。
结果
THSWD 可显著降低神经功能评分（P<0.01）和脑组织神经元损伤，增加脑组织 Claudin-5 和 zonula occludens-1（ZO-1）蛋白表达（P<0.01），降低血清脂多糖（LPS）（P<0.01）、二胺氧化酶（DAO）（P<0.01）和 D-乳酸（P<0.01，P<0.05）水平。THSWD 还抑制了脑组织肿瘤坏死因子-α（TNF-α）（P<0.01）和白细胞介素-1β（IL-1β）（P<0.01）的水平，并增加了缺血性中风小鼠的α和β多样性，对不同的微生物群具有一定的逆转作用。最后，THSWD 抑制了小胶质细胞的极化（P<0.01），降低了脑组织 toll 样受体-4（TLR-4）（P<0.01，P<0.05）和核因子 kappa B（NF-κB）（P<0.01）的蛋白和基因表达。
结论
我们的数据表明，THSWD 可能通过调节肠道菌群和促进肠道屏障修复来干扰缺血性中风的炎症反应。
Zotero 插件