PPARα/γ激动剂对糖尿病伴冠心病患者血浆炎症因子的影响

Effects of PPAR α/γ dual agonists on plasma inflammatory cytokine in patients with diabetes complicated with coronary artery disease

目的探讨联合应用过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)α/γ激动剂对糖尿病伴冠状动脉粥样硬化性心脏病(冠心病)患者血浆炎症因子的影响。方法将80例伴有糖尿病的冠心病患者分为马来酸罗格列酮组(n=20)、苯扎贝特组(n=20)、马来酸罗格列酮和苯扎贝特联合组(n=20)、常规治疗组(n=20)。治疗后,对所有患者随访12周。治疗前后均对所有患者采血,并用酶联免疫吸附法测定患者血浆C反应蛋白、单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1),观察患者空腹血糖、空腹胰岛素、胰岛素抵抗指数、糖化血红蛋白-A1c(HbA1c)、血脂、体质量指数的改变。结果联合组、马来酸罗格列酮组、苯扎贝特组血浆C反应蛋白、MCP-1、空腹血糖、糖化血红蛋白、胰岛素、总胆固醇、三酰甘油、低密度脂蛋白胆固醇浓度和胰岛素抵抗指数治疗12周后比治疗前明显降低,高密度脂蛋白胆固醇明显升高,差异有统计学意义(P<0.05),且联合组上述指标改善最显著。马来酸罗格列酮组、苯扎贝特组、联合组的单核细胞在脂多糖诱导下分泌MCP-1浓度较治疗前降低,以联合组降低最为显著。C反应蛋白的降低与空腹胰岛素和胰岛素抵抗指数的降低呈正相关(r=0.498,P<0.001和r=0.496,P<0.001),与其他因素的变化无相关性(P>0.05);而MCP-1的变化与糖、脂代谢无相关性(P>0.05);C反应蛋白与MCP-1之间也无明显相关性(P>0.05)。结论联合应用马来酸罗格列酮、苯扎贝特能够降低血浆C反应蛋白和MCP-1浓度,降低血糖和血浆胰岛素浓度,减轻胰岛素抵抗,改善辛伐他汀治疗后残存的高三酰甘油和低高密度脂蛋白胆固醇,效果优于单用马来酸罗格列酮或苯扎贝特。

Objectives To observe the effects of combined peroxisome proliferator-activated receptor （PPAR） α-agonist and PPARΥ-agonist on plasma concentrations of inflammatory cytokine in patients with diabetes mellitus complicated with coronary artery disease （CAD）. Methods Eighty CAD patients were divided into four groups： rosiglitazone group （n=20）, bezafibrate group （n=20）, combination of rosiglitazone and bezafibrate group（n=20） and control group （n= 20）. After treatment, patients were followed-up for 12 weeks. Plasma sample was collected from each patient before and after the treatment, respectively. Then plasma concentrations of C-reactive protein （CRP） and monocyte ehemoatactic protein-1 （MCP-1） were measured by enzyme-linked immunosorbent assay. At the same time, the changes of fasting plasma glucose （FPG）, fasting insulin, insulin resistance index （IRI）, hemoglobin Ale （HbAle）, lipid and body mass index were also investigated. Results At the end of 12 weeks, patients in rosiglitazone group, bezafibrate group and combined rosiglitazone and bezafibrate group showed significantly reduction in plasma concentrations of CRP, MCP-1, FPG, insulin, IRI, HbAlc, triglyeerides, total cholesterol, low-density lipoprotein cholesterol, and increasion in concentration of high-density lipoprotein cholesterol （P〈O.05）, especially in combined rosiglitazone and bezafibrate group. Concentrations of MCP-1 secreted by monoeyte which was induced by lipopolysaccharide in rosiglitazone group,bezafibrate group and combined rosiglitazone and bezafibrate group were siginificantly higher after 12 weeks treatment than those before treatment （P〈0.05）, and the decrease was most obviously in combined rosiglitazone and bezafibrate group. Decline in plasma concentrations of CRP appear to be correlated with the decrease of insulin （r=0.048, P〈0.01 ） and insulin resistance index （r=0.496,P〈0.001）, but there was no correlation with other factors. Conclusions Combination of rosiglitazone and bezafibrate can increase insulin sensitivity, improve glucose metabolism and reduce the concentrations of CRP, MCP-1 in patients with diabetes mellitus complicated with CAD. The effects of combination are more obvious than single drug.