Berberine protects against lipopolysaccharide- induced intestinal injury in mice via alpha 2 adrenoceptor-independent mechanisms  

作　　者：Hong-mei LI Yi-yang WANG Hua-dong WANG Wen-juan CAO Xiao-hui YU Da-xiang LU Ren-bin QI Chao-feng HU Yu-xia YAN 

机构地区：[1]Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine, School of Medicine, Ji-nan University, Guangzhou 510632, China [2]Institute of Integrative Medicine, Ji-nan University, Guangzhou 510632, China [3]Department of Biochemistry, School of Medicine, Ji-nan University, Guangzhou 510632, China

出　　处：《Acta Pharmacologica Sinica》2011年第11期1364-1372,共9页中国药理学报（英文版）

摘　　要：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/lO 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-KBa （I-KBa） 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 intesti- nal villus height, reduced gut mucosal weight and increased intestinal permeability. Furthermore, LPS significantly induced entero- cyte apoptosis, increased TLR4 mRNA expression, I-KBa 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 a2-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 entero- cyte apoptosis, inhibiting the TLR4-nuclear factor KB-MIP-2 pathway and decreasing neutrophil infiltration that are independent of a2-adrenoceptors.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/lO 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-KBa （I-KBa） 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 intesti- nal villus height, reduced gut mucosal weight and increased intestinal permeability. Furthermore, LPS significantly induced entero- cyte apoptosis, increased TLR4 mRNA expression, I-KBa 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 a2-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 entero- cyte apoptosis, inhibiting the TLR4-nuclear factor KB-MIP-2 pathway and decreasing neutrophil infiltration that are independent of a2-adrenoceptors.

关 键 词：BERBERINE LIPOPOLYSACCHARIDE intestinal injury apoptosis Toll-like receptor 4 （TLR4） NF-KB macrophage inflammatoryprotein-2 （MIP-2） a2-adrenoceptor YOHIMBINE 

分 类 号：Q577[生物学—生物化学] S858.287.3[农业科学—临床兽医学]