期刊
ACTA PHARMACOLOGICA SINICA
卷 32, 期 11, 页码 1364-1372出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/aps.2011.102
关键词
berberine; lipopolysaccharide; intestinal injury; apoptosis; Toll-like receptor 4 (TLR4); NF-kappa B; macrophage inflammatory protein-2 (MIP-2); alpha(2)-adrenoceptor; yohimbine
资金
- National Natural Science Foundation of China [30670826, 30971191]
- Science and Technology Foundation from the Ministry of Education of the People's Republic of China [207140]
- Guangdong Science and Technology Projects [2008B030301352]
- Ji-nan University
Aim: To investigate the mechanisms responsible for the protective action of berberine (Ber) against gut damage in endotoxemic mice. Methods: Male BALB/c mice were administered intragastrically with distilled water (0.1 mL/10 g), Ber (50 mg/kg) alone, yohimbine (2 mg/kg) alone, or Ber (50mg/kg) in combination with yohimbine (2 mg/kg) for 3 d. On the third day, lipopolysaccharide (LPS, 18 mg/kg) or normal saline was intraperitoneally injected one hour after the intragastric administration. Following the treatment, intestinal injury in the ileum was histopathologically accessed; enterocyte apoptosis was examined using TUNEL method; Toll-like receptor 4 (TLR4) mRNA expression was measured using RT-PCR assay; inhibitor protein-kappa B alpha (I-kappa B alpha) phosphorylation and myeloperoxidase content were examined using Western blloting. The macrophage inflammatory protein-2 (MIP-2) production was measured using ELISA assay. Results: Mice challenged with LPS caused extensive ileum injury, including a significantly increased injury score, decreased intestinal villus height, reduced gut mucosal weight and increased intestinal permeability. Furthermore, LPS significantly induced enterocyte apoptosis, increased TLR4 mRNA expression, I-kappa B alpha phosphorylation, MIP-2 production and myeloperoxidase content in the ileum. Pretreatment with Ber significantly alleviated all the alterations in the ileum in the endotoxemic mice. Pretreatment with the alpha(2)-adrenoceptor antagonist yohimbine did not block the protective action of Ber against LPS-induced intestinal injury. In addition, treatment with yohimbine alone did not prevent LPS-induced intestinal injury. Conclusion: Pretreatment with Ber provides significant protection against LPS-induced intestinal injury in mice, via reducing enterocyte apoptosis, inhibiting the TLR4-nuclear factor kappa B-MIP-2 pathway and decreasing neutrophil infiltration that are independent of alpha 2-adrenoceptors.
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