罗格列酮对高糖诱导大鼠胸主动脉血管平滑肌细胞分泌单核细胞趋化蛋白1的影响及其机制

目的观察不同葡萄糖浓度培养的大鼠胸主动脉平滑肌细胞分泌单核细胞趋化蛋白1（MCP-1）的变化，以及罗格列酮（RGZ）对其分泌的影响。方法用不同浓度的葡萄糖和RGZ单独或联合孵育大鼠胸主动脉平滑肌细胞，用ELISA方法检测培养基中MCP-1的水平，Western Blot方法检测各组所收集细胞胞浆中NF-κBp65和IκBα的表达。结果高葡萄糖浓度培养（11．2，22．4mmol／L）的大鼠胸主动脉平滑肌细胞分泌的MCP-1分别为（340．87±43．92）pg／ml和（664．87±23．07）pg／m1]明显高于对照组-（132．20±5．81）pg／ml]，RGZ抑制了高葡萄糖孵育下大鼠胸主动脉平滑肌细胞MCP-1蛋白表达水平并呈浓度依赖性，RGZ拮抗剂GW9662（10μmol／L）预处理可部分拮抗其作用。MCP-1水平的变化与细胞浆NF-κB、IκB的表达变化相伴随。结论高糖可以诱导大鼠胸主动脉平滑肌细胞分泌MCP-1，并呈现浓度依赖性；RGZ可抑制高糖诱导的大鼠胸主动脉平滑肌细胞分泌MCP-1水平，上述作用在一定浓度范围内呈现剂量依赖性。高糖诱导平滑肌细胞分泌MCP-1很可能是通过NF-κB通路来调控的。

Effect and its mechanism of rosiglitazone on MCP-1 secretion of rat thoracic aorta smooth muscle cells induced by high-glucose

Objective To observe the MCP-1 secretion of rat thoracic aorta VSMCs incubated with different concentration of glucose and effects of rosiglitazone （RGZ）. Methods The rat thoracic aorta VSMCs were incubated with different concentration of glucose alone or with different concentration of glucose and rosiglitazone, the concentration of MCP-1 in the supernatant was measured with the method of enzyme linked immunoabsorbent assay（ELISA）. The levels of NF-κB and IκB protein in the aliquots of the cell extract were examined by Western blot. Results The supernatant concentration of MCP-1 in high glucose group（11.2, 22.4mmool/L）was significantly higher than in control group （P〈0. 01）. They were （340. 87±43.92）pg/ml and （664.87±23.07）pg/ml respectively, and the level of control group was only （132.20±5.81）pg/ml. Rosiglitazone significantly inhibited MCP-1 secretion in rat thoracic aorta VSMCs induced by high glucose in a concentration-dependent manner. RGZ antagonist GW9662 （10μmol/L） partly inhibited the effects of RGZ. The changes of MCP-1 level were accompanied by the changes of NF- κB and IκB. Conclusions High glucose could increase the secretion of MCP-1 in cultured rat thoracic aorta VSMCs and this effect depends on concentration in some extent. Rosiglitazone could inhibit the level of MCP-1 in rat thoracic aorta VSMCs induced by high glucose in a dose-dependent manner. The secretion of MCP-1 in VSMCs induced by high glucose may be regulated by NF-κB signal pathway.