【作者】 陈峰；

【导师】 张赛丹；

【作者基本信息】 中南大学 ， 内科学， 2007， 硕士

【摘要】 目的：探讨高脂血症患者MCP-1与肱动脉血流介导的内皮依赖性舒张功能(FMD)的关系，并且观察辛伐他汀对高脂血症患者MCP-1和FMD的影响。方法：选择高脂血症患者58例，健康人26例。采用SONOS5500型超声心动图仪检测肱动脉基础状态下及反应充血时(内皮依赖性舒张)的内径。采用ELISA酶联法检测血清MCP-1浓度。入选患者随机分为治疗组(30例)，推荐低脂饮食基础上给予辛伐他汀20mg／d，疗程8周；对照组(28例)，推荐低脂饮食治疗8周；设正常组(26例)。治疗前后常规检测血脂TG、TC、LDL、HDL浓度。结果：治疗前对照组和治疗组FMD分别为6.46％±1.21％和6.31％±1.16％，与正常组13.62％±0.77％比较有统计学意义(P＜0.05)。治疗前对照组和治疗组MCP-1浓度分别174.89±25pg／ml和171.13±24pg／ml与正常对照组110.66±14pg／ml比较均有统计学意义(P＜0.05)。直线相关分析显示，高脂血症患者MCP-1与TC及LDL显著正相关(r为0.502及0.705，P值均＜0.05)。MCP-1与肱动脉血流介导扩张(FMD)之间呈负相关(r=-0.562，P＜0.001)。经8周辛伐他汀治疗后发现，治疗组TC和LDL显著降低(P＜0.05)，肱动脉血流介导扩张(FMD％)显著增高，由6.31％±1.16％增至12.21％±1.31％，差异有统计学意义(P＜0.05)；MCP-1浓度较治疗前显著降低，由171.13±24pg／ml降至110.75±16pg／ml，差异亦有统计学意义(P＜0.05)。对照组治疗8周后，血脂无显著降低(P＞0.05)，FMD较治疗前有所改善，由6.46％±1.21％增至6.98±1.23％，但差异无统计学意义(P＞0.05)；MCP-1浓度由174.89±25pg／ml降至164.57±30pg／ml(P＞0.05)。治疗8周末，治疗组FMD 12.21％±1.31％明显高于对照组6.98％±1.23％，差异有统计学意义(P＜0.05)。治疗组MCP-1浓度110.75±16pg／ml显著低于对照组164.57±30pg／ml，差异亦有统计学意义(P＜0.05)。辛伐他汀治疗后血管内皮功能FMD的增高程度与血脂TC、LDL降低程度无显著相关(r分别为-0.110和0.022，P值均＞0.05)。结论：1．高脂血症患者血管内皮依赖性舒张功能减退2．高脂血症患者MCP-1水平增高与血管内皮依赖性舒张功能受损有关。3．辛伐他汀治疗8周后对于高脂血症患者的血管内皮依赖性舒张功能的改善可能部分独立于降脂作用之外。4．辛伐他汀抗动脉粥样硬化作用可能部分与减少炎症因子MCP-1释放及血管内皮功能的改善有关。更多还原

【Abstract】 Objective: To investigate the effects of simvastatin therapy onvascular endothelial fuction and monocyte chemoattractant protein-1(MCP-1) in patients with hyperlipidemia.Methods: 58 patients with hyperlipidemia were randomly dividedinto two groups: control group(28 patients) and simvastatin therpygroup(30 patients,simvastatin 20mg daily for 8 weeks).26 normal healthysubjects were acted as the normal control group. In order to assess thefuction of vascular endothelium by the flow-mediated dilatation (FMD)ofbraehial artery which can be evaluated using high resolution ultralsoundassessment of the brachial artery diameter. The enzyme-linked immunosorbent Assay(ELISA) examined the level of serum MCP-1 before andafter diet or drug therapy. Total cholesterol(TC)、triglyceride(TG)、lowdensity lipoprotein (LDL)and high density lipoprotein(HDL) for eachgroup were measured.Results: Flow-mediated dilation(FMD) in the control group6.46%±1.21% and simvastatin therpy group 6.31%±1.16% weresignificantly lower than that in the normal group 13.62%±0.77% beforestatin therapy (P＜0.05).The serum MCP-1 in the control group174.89±25pg/ml and simvastatin therpy group 171.13±24pg/ml weresignificantly higher than that in the normal group 110.66±14pg/ml before statin therapy (P＜0.05).The serum MCP-1 was positively related to theserum level of TC (r=0.502,P＜0.05) or LDL(r=0.705,P＜0.05)and FMDwas inversely related to the serum level of MCP-1 (r=-0.562,P＜0.001) inall patients with hyperlipidemia. After 8-week treatment with simvastatin,TC and LDL were decreased significantly(P＜0.05),FMD was increasedfrom 6.31%±1.16% to 12.21%±1.31% (P＜0.05)and MCP-1 wasdecreased from 171.13±24pg/ml to 110.75±16pg/ml(P＜0.05).Aftereight-week treatment with diet control, there were no significant changesof the TC、LDL and FMD and MCP-1(P＞0.05).At the end point oftreatment, FMD was increased in the simvastatin therpy group12.21%±1.31% than in the control group 6.98%±1.23% (P＜0.05)andthe level of mcp-1 was lower in the simvastatin therpy group110.75±16pg/ml than in the control group164.57±30pg/ml (P＜0.05).Aftereight-week therapy, the reduction of serum TC or LDL level was notcorrelated with the improvement of FMD (r=-0.110 and 0.022, P＞0.05).Conclusions: The brachial artery endothelium-dependent dilationwas decreased in patients with hyperlipidemia. The increased serum levelof MCP-1 is correlated with the brachial artery endothelium-dependentdilation dysfunction in patients with hyperlipidemia. Simvastatin couldimproved endothelial function in addition to its lipid-lowering effectpartly. Anti-atherosclerosis’s effect of simvastatin may be partly involvedin the reduction of inflammatory marker levels and the improved endothelial function.更多还原