小白菊内酯对硝基酪氨酸诱导的肾小球系膜细胞核转录因子-κB和单核细胞趋化蛋白-1表达的影响  

Effect of Parthenolide on Nitrotyrosine-Induced NF-κB Activation and Monocyte Chemoattractant Protein-1 Expression in Rat Mesangial Cells

作　　者：王建成[1] 贾倩倩[1] 赵艳[1] 陈斯佳[1] 龙海波[1] 

机构地区：[1]南方医科大学珠江医院肾内科,广东广州510280

出　　处：《中国药业》2013年第19期7-9,共3页China Pharmaceuticals

基　　金：国家自然科学基金项目;项目编号:81072848;广东省科技计划项目;项目编号:2011B061300014

摘　　要：目的观察小白菊内酯(PTL)对硝基酪氨酸(NT)诱导的大鼠肾小球系膜细胞核转录因子-κB(NF-κB)及单核细胞趋化蛋白-1(MCP-1)表达的影响。方法通过体外培养的系膜细胞进行研究。设立低糖对照组(糖浓度为5.6 mmol/L)、NT试验组(100μmol/L)及吡咯二流氨基甲酸酯(PDTC)干预组(100μmol/L)和含PTL(1,5,10μmol/L)的干预组。以实时荧光定量PCR检测MCP-1 mRNA的表达;用酶联免疫(ELISA)法检测培养细胞上清中MCP-1;Western Blot方法检测系膜细胞核内NF-κB p65蛋白的表达。结果 NT诱导系膜细胞24 h后,MCP-1分泌明显增强(P<0.01),小白菊内酯(1,5,10μmol/L)对NT诱导的系膜细胞分泌的MCP-1的抑制作用随浓度增大而逐渐增强。系膜细胞在低浓度葡萄糖作用下可低水平表达MCP-1 mRNA,NT作用24 h后MCP-1 mRNA表达明显增强(P<0.01),PTL可明显下调NT诱导的MCP-1 mRNA表达(P<0.01)。在NT作用1 h后,系膜细胞核内的NF-κB p65蛋白核内表达增强(P<0.05),PTL能部分抑制NT诱导的系膜细胞NF-κB p65进入细胞核内(P<0.05)。结论在体外含NT培养条件下,小白菊内酯可部分逆转NT诱导的系膜细胞NF-κB p65进入细胞核内,进一步抑制MCP-1 mRNA及蛋白在系膜细胞的表达,提示小白菊内酯对MCP-1的影响可能与NF-κB的抑制有关。Objective To observe the effect of parthenolide（PTL） on nitrotyrosine（NT） induced nuclear factor-κB（NF-κB） activation and monocyte chemoattractant protein- 1 （MCP- 1 ） expression in rat mesangial cells（MCs）. Methods MC cells were cultured in vitro. The low glucose control group （low glucose concentration of 5.6 mmol/L）, the NT test group（100 μmol/L）, the pyrrolidine dithiocar- bamate （PDTC） intervention group （100 μmol/L） and the PTL intervention groups （containing PTL 1, 5, 10 μmol/L respectively） were set up. The enzyme- linked immunoabsorbent assay （ELISA） method was adopted to detect MCP- 1 protein in the supernatant and the expression of NF- κB p65 protein in cell nucleus was detected by Western Blot. Results The MCP- 1 protein secretion was enhanced obviously after NT inducing MCs for 24 h（P 〈0.01）, the inhibiting effect of PTL（1, 5, 10 μmol/L） on MCP-1 se- creted by NT induced MCs was gradually enhanced with the concentration increase. MCs could express MCP- 1 mRNA in the low level under the low glucose action. MCP- 1 mRNA expression was enhanced obviously after NT action for 24 h （P 〈 O. 01）. PTL could obviously down-regulate NT induced MCP-1 mRNA expression（P〈 0.01）. The expression of NF-κB p65 protein in the eel1 nucleus was enhanced after NT action for l h （P 〈 0. 05）. PTL can partially restrain NT- induced NF- κB p65 to enter into cell nucleus（ P 〈 0. 05）. Conclusion PTL can partially reverse NT- induced NF- κB p65 to enter into cell nucleus, further inhibit the expression of MCP- 1 mRNA and protein in MCs, which indicating that the influence of PTL on MCP- 1 may be related with the inhibition of NF- κB.

关 键 词：小白菊内酯 核转录因子-ΚB 单核细胞趋化蛋白-1 硝基酪氨酸 

分 类 号：R285.5[医药卫生—中药学] R282.71[医药卫生—中医学]