罗格列酮对高糖环境中大鼠系膜细胞活性氧及单核细胞化学吸引蛋白质1的抑制作用  

Inhibitory effects of rosiglitazone on the synthesis of reactive oxygen species and the expression of monocyte chemoattractant protein 1 in rat mesangiai cells cultured in high glucose

作　　者：包艳[1] 贾汝汉[2] 李竞[1] 袁军[2] 孙永林[1] 王颖[1] 

机构地区：[1]武汉大学人民医院内分泌科,430060 [2]武汉大学人民医院肾内科,430060

出　　处：《中华肾脏病杂志》2009年第1期48-52,共5页Chinese Journal of Nephrology

摘　　要：目的观察罗格列酮对高糖培养基中大鼠系膜细胞活性氧（ROS）及单核细胞化学吸引蛋白质1（MCP-1）mRNA、蛋白表达的抑制作用，并探讨相关机制。方法将培养的大鼠系膜细胞分为以下6组：对照组（C组，普通MEM培养基，含5．6mmol／L葡萄糖）、甘露醇组（M组，24．2mmol／L甘露醇＋C组）、高糖组（H组，30mmol／L高糖MEM培养基）、小剂量罗格列酮干预组（R1组，H组＋10μmol／L罗格列酮）、大剂量罗格列酮干预组（R2组，H组＋20μmol／L罗格列酮）、N-乙酰半胱氨酸（NAC）干预组（N组，H组＋5mmol／LNAC）。采用激光共聚焦法检测ROS水平，分别采用RT，PCR和ELISA法检测MCP-1 mRNA及蛋白含量。结果C组和M组间ROS、MCP-1的表达差异无统计学意义，H组ROS水平较C组增高4．1倍（P〈0．01），分别采用罗格列酮（20μmol／L）和NAC干预后，ROS水平显著降低（P〈0．01）；罗格列酮（20μmol／L）和NAC均可显著抑制高糖环境中MCP-1 mRNA的高表达（P〈0．01）。H组中MCP-1蛋白水平[（940．9±20．3）ng／L]显著高于C组[（403．0±8．1）ng／L1（P〈0．01），而R2组和N组的MCP-1蛋白水平[（562．5±15．3）ng／L，（539．8±8．3）ng／L]显著低于H组（P〈0．01）。结论罗格列酮可通过减少ROS而降低高糖所诱导的MCP-1表达，而这可能是罗格列酮发挥直接肾脏保护作用的机制之一。Objective To investigate the inhibitory effects of rosiglitazone on the synthesis of reactive oxygen species （ROS） and the expression of monocyte chemoattractant protein 1 （MCP-1） induced by high glucose in rat mesangial cells. Methods The mesangial cells were divided into six groups： control group （ C, 5.6 mmol/L glucose）, mannitol group （M, 24.2 mmol/L mannitol＋group C）, high glucose group（ H, 30 mmol/L glucose）, R1 group（R1, group H＋10 μmol/ L rosiglitazone）, R2 group （R2, group H＋20 μmol/L rosiglitazone）, N-acetylcysteine （NAC） group （N, group H＋5 mmol/L NAC, NAC was added 1 h before the stimulation of high glucose）. The level of ROS was measured by confocal laser scanning microscopy. The mRNA and the protein expression of MCP-1 were semi-quantitatively determined with reverse transcription-polymerase chain reaction and ELISA respectively. Results No significant differences of ROS and MCP-1 were found between control group and mannitol group. The intracellular ROS induced by high glucose increased by 4.1-fold compared to control group （P〈0.01）, which was prevented by rosiglitazone （20 μmol/L） and NAC respeetively. The MCP-1 mRNA expression in group R2 and group N was significantly lower than that in group H （P〈0.01）. The MCP-1 protein level in group H [（940.9±20.3） ng/L] was higher than that in group C [（403.0±8.1） ng/L] （P〈0.01）, and the expression of MCP-1 protein in group R2 [（562.5±15.3） ng/L] and group N [（539.8±8.3） ng/L] was lower than that in group H （P〈0.01）. Conclusion Rosiglitazone may suppress high glucose-induced MCP-I expression by reducing the level of ROS, which may be one of the mechanisms that rosiglitazone plays a direct role in the proteetion of kidney.

关 键 词：活性氧 趋化因子CCL2 系膜细胞 罗格列酮 

分 类 号：R96[医药卫生—药理学]