中文摘要：

目的：观察小檗碱和α2肾上腺素能受体拮抗剂育亨宾对内毒素血症小鼠脾脏Toll样受体4（TLR4）信号通路84种基因表达的影响,并初步探讨其作用机制。方法：雄性BALB/c小鼠随机分为对照组、脂多糖（LPS）组、小檗碱＋LPS组、小檗碱＋育亨宾＋LPS组、育亨宾＋LPS组、小檗碱组、小檗碱＋育亨宾组和育亨宾组。分别用蒸馏水、小檗碱（50 mg/kg）、小檗碱＋育亨宾（50 mg/kg＋2 mg/kg）和育亨宾（2 mg/kg）灌胃,每天1次,连续3 d,第3 d灌胃1 h后,腹腔注射LPS（20 mg/kg）或生理盐水。腹腔注射1 h后,用RT2ProfilerTMPCR Array分析技术检测小鼠脾脏TLR4信号通路84种基因mRNA的表达;用Western blotting分析小鼠脾脏TLR4信号通路的抑制分子细胞因子信号抑制物（SOCS）1、SOCS3和白细胞介素-1受体相关激酶（IRAK）-M蛋白的表达。结果：LPS可上调小鼠脾脏TLR4信号转导通路中相关炎症因子的mRNA表达,包括CXCL10、TNF-α、IL-1α、IL-1β、IL-6、IFN-γ和IFN-β。小檗碱能显著下调下调髓样分化因子（MyD88）依赖信号通路下游TNF-α、IL-1α、IL-1β和IL-6 mRNA的表达,也能MyD88非依赖信号通路下游基因IFN-β和CXCL10 mRNA的表达（P〈0.05）。育亨宾能显著下调内毒素血症小鼠脾脏IL-1α、IL-1β和IFN-βmRNA的表达（P〈0.05）,但对TNF-α、IL-6和CXCL10 mRNA表达的下调作用与LPS组相比没有显著差异（P〉0.05）。小檗碱与育亨宾合剂能显著下调内毒素血症小鼠脾脏IFN-β和CXCL10 mRNA的表达,但不能显著下调内毒素血症小鼠脾脏IL-1α、IL-1β、TNF-α和IL-6 mRNA的表达。LPS攻击后1 h,小檗碱和（或）育亨宾均不能增强内毒素血症小鼠脾脏SOCS1、SOCS3和IRAK-M蛋白的表达。结论：小檗碱和育亨宾均能抑制LPS诱导的MyD88依赖和非依赖信号通路下游部分基因的表达,这种抑制作用的机制与SOCS1、SOCS3和IRAK-M蛋白无关。

英文摘要：

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 RT2 ProfilerTM PCR Array.Moreover,the protein expression of suppressor of cytokine signaling（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-1β,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-β and CXCL10,which were in the downstream of MyD88-independent signaling pathway（P0.05）.Y markedly inhibited the mRNA expression of IL-1α,IL-1β and IFN-β in the spleen of endotoxemic mice（P0.05）,but did not affect the mRNA expression of TNF-α,IL-6 and CXCL10（P0.05）.Combination of Ber with Y significantly reduced the mRNA expression of IFN-β 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 SOCS1,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-de