白藜芦醇调控大鼠急性肺栓塞后肺动脉高压及MCP-1表达的机制研究  

Resveratrol down-regulates acute pulmonary thromboembolism-induced pulmonary artery hypertension and monocyte chemoattractant protein-1 in rats

作　　者：陈淳[1] 林建伟 李国平[3] 任卓超[1] 李亚清[1] 严建平[1] 王良兴[4] 

机构地区：[1]浙江省人民医院呼吸内科杭州医学院附属人民医院呼吸内科,浙江杭州310014 [2]浙江大学附属邵逸夫医院心血管内科,浙江杭州310014 [3]浙江省立同德医院呼吸内科,浙江杭州310012 [4]温州医科大学附属第一医院呼吸内科,浙江温州325000

出　　处：《中国药理学通报》2017年第10期1436-1441,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30871138)

摘　　要：目的观察单核细胞趋化蛋白1(monocyte chemoattractant protein 1,MCP-1)与急性肺栓塞(pulmonary thromboembolism,PTE)后肺动脉高压形成的关系;探讨中药单体白藜芦醇调控急性PTE后肺动脉高压及其对MCP-1表达的影响及机制。方法采用自体血栓回输法复制Sprague-Dawley大鼠急性PTE模型;将大鼠随机分成5组(正常组、溶剂组、急性PTE组、抗体Cl142组、白藜芦醇组),每组观察1、4、8 h3个时点;急性PTE模型复制前1 h,分别对MCP-1中和抗体C1142组及白藜芦醇组进行药物预处理;在1、4、8 h时间点检测各组肺动脉平均压力(mean pulmonary artery pressure,MPAP)和MCP-1 mRNA及蛋白表达情况。结果 (1)在相同时点,急性PTE组MPAP和MCP-1 mRNA、蛋白表达均较溶剂对照组明显升高(P<0.05);(2)在相同时点,白藜芦醇组MPAP和MCP-1 mRNA、蛋白表达较急性PTE组明显降低(P<0.05);(3)在相同时点,抗体C1142组MCP-1 mRNA、蛋白表达较急性PTE组明显降低(P<0.05)。结论急性PTE后MCP-1的大量表达参与急性PTE后肺动脉高压的形成,白藜芦醇可通过下调MCP-1表达,降低急性PTE后肺动脉压力。Aim To investigate the relationship between monocyte chemoattractant protein-1（ MCP-1）and pulmonary artery hypertension after acute pulmonary thromboembolism（ PTE）,and to explore the effects and mechanisms of resveratrol with MCP-1 in the acute PTE as well. Methods The acute PTE model of Sprague-Dawley rats was replicated using self-thrombosis.The rats were randomly divided into five groups（ Normal,Solvent,acute PTE,antibody Cl142,and resveratrol）,and 1h,4h,8h and 3 points were observed in each group. A model of acute PTE was established by infusion of an autologous blood clot into the pulmonary artery through a polyethylene catheter. Resveratrol or Cl142,dissolved in 1% dimethyl sulfoxide（ DMSO）,was administered to the animals through caudalvein 1 h prior to the beginning of acute PTE modeling. Rats in normal control group and solvent control group were injected with normal saline and 1% DMSO respectively. The mean pulmonary artery pressure（ MPAP） and the mRNA and protein expression of MCP-1 were measured at each time point. Results（1）The acute PTE group MPAP,MCP-1 mRNA and protein expression were significantly higher than those of the control group（ P 〈0. 05） at the same time;（2） The resveratrol group＇ s MPAP and MCP-1 mRNA,protein expression were significantly lower than those of the acute PTE group（ P 〈0. 05） at the same time;（3） The Cl142 group MPAP and MCP-1 mRNA,protein expression were markedly reduced in the acute PTE group（ P 〈0. 05） at the same time. Conclusions The large expression of MCP-1 after acute PTE is involved in the formation of pulmonary hypertension after acute PTE.Resveratrol can reduce the pressure of pulmonary artery after acute PTE by down-regulating the MCP-1 expression.

关 键 词：白藜芦醇 急性肺栓塞 肺动脉高压 单核细胞趋化蛋白-1 炎症因子 炎症反应 

分 类 号：R-332[医药卫生] R284.1