中国病理生理杂志2012，Vol.28Issue(4)：655-663,9.DOI:10.3969/j.issn.1000-4718.2012.04.014
小檗碱和育亨宾对内毒素血症小鼠脾脏TLR4信号通路中相关基因表达的影响
Effect of berberine and yohimbine on TLR4-dependent gene expression in spleen of endotoxemic mice
摘要
Abstract
AIM: To investigate the effects of berberine ( Ber) and yohimbine ( Y) on gene expression in Toll - like receptor 4 (TLR4) signaling pathways in the spleen of endotoxemic mice . METHODS: The male BALB/c mice were randomly divided into the following groups: control, lipopolysaccharides ( LPS) , Ber + LPS, Y + Ber + LPS, Y + LPS, Ber, Y + Ber and Y alone. The mice were treated with water , Y (2 mg/kg) or/and Ber (50 mg/kg) intragastrically once a day for 3 days , and then injected intraperitoneally with normal saline or LPS (20 mg/kg) 1 h after intragastrical treatment on day 3. One hour after LPS challenge , the expression changes of 84 genes in TLR4 signaling pathways in the spleen of the mice were examined using RT Profiler PCR Array. Moreover, the protein expression of suppressor of cytokine signa -ling (SOCS) 1, SOCS3 and IL - 1 receptor - associated kinase (IRAK) - M in the spleen was examined using Western blotting. RESULTS: LPS induced the expression of multiple downstream inflammatory mediators in myeloid differentiation factor 88 (MyD88) - dependent and independent signaling pathways , such as TNF -α, IL-1α, IL - 1 β, IL-6, IFN -γ, IFN - β and CXCL10. Ber not only down - regulated LPS - induced mRNA expression of TNF -α, IL - 1β, L - 1β and IL - 6, which were in the downstream of MyD88 - dependent signaling pathway , but also reduced LPS - stimulated mRNA expression of IFN - (3 and CXCL10, which were in the downstream of MyD88 - independent signaling pathway (P < 0. 05 ). Y markedly inhibited the mRNA expression of IL - lα, IL - 1 (3 and IFN - (3 in the spleen of endotoxemic mice (P < 0. 05) , but did not affect the mRNA expression of TNF - α, IL - 6 and CXCL10 (P > 0. 05 ). Combination of Ber withY significantly reduced the mRNA expression of IFN - (3 and CXCL10 in the spleen of the mice challenged with LPS. One hour after LPS challenge , Ber or/and Y did not increase the protein expression of SOCS 1 , SOCS3 and IRAK - M in the spleen of the mice. CONCLUSION; Pretreatment with Ber and Y down - regulates the expression of some genes in the downstream of MyD88 - dependent and MyD 88 - independent signal pathways in the spleen of endotoxemic mice . The mechanism of these actions is not related with SOCS 1, SOCS3 and IRAK - M at protein level.关键词
小檗碱/育亨宾/内毒素血症/Toll样受体4/小鼠Key words
Berberine/Yohimbine/Endotoxemia/Toll-like receptor 4/Mice分类
医药卫生引用本文复制引用
李辉,王一阳,李红梅,王发强,吕秀秀,戚仁斌,陆大祥,王彦平,王华东..小檗碱和育亨宾对内毒素血症小鼠脾脏TLR4信号通路中相关基因表达的影响[J].中国病理生理杂志,2012,28(4):655-663,9.基金项目
国家自然科学基金资助项目(No.30670826 （）
No.30971191) （）
教育部科学技术研究重点项目(No.207140) （No.207140）
广东省科技计划项目(No.2008B030301352,粤科计字[2008]144 号) （No.2008B030301352,粤科计字[2008]144 号）
