普伐他汀对高胆固醇血症患者CD40配体的影响

Effect of Pravastatin on Platelet CD40L and Soluble CD40L in Patients with Hypercholesterolemia

目的:观察高胆固醇血症患者血小板膜CD40配体(CD40L)和血浆可溶性CD40L(sCD40L)的表达以及普伐他汀对CD40L等的影响,探讨高胆固醇血症促动脉粥样硬化炎症反应、血栓形成的机制。方法:选择高胆固醇血症患者40例及年龄、性别相匹配的健康对照组20例,采用流式细胞术测定血小板膜CD40L,酶联免疫吸附法(ELISA)测定sCD40L、血浆单核细胞趋化蛋白-1(MCP-1)水平及凝血酶原片段1+2(F1+2)。高胆固醇血症患者随机分成普伐他汀组(A组,n=20)及饮食控制组(B组,n=20),A组普伐他汀20mg/天治疗,B组只作饮食控制,7天后分别测定以上指标。结果:高胆固醇血症患者血小板膜CD40L表达,血浆sCD40L、MCP-1、F1+2水平明显高于对照组(P均<0.01),且sCD40L与血小板膜CD40L、血清TC、LDL-C及血浆MCP-1、F1+2呈显著正相关(r值分别为0.66、0.52、0.51、0.63和0.61,P均<0.05)。普伐他汀短期治疗后,A组血小板膜CD40L、血浆sCD40L、MCP-1、F1+2显著降低(P均<0.05),而血脂无显著变化。结论:高胆固醇血症患者血小板膜表达CD40L及sCD40L增高,高胆固醇血症可能通过激活CD40L促进炎症反应、血栓形成而参与AS的发生发展。普伐他汀可不依赖血浆胆固醇水平的降低而抑制血小板膜表达CD40L和sCD40L及由CD40L介导的AS的炎症反应和血栓形成。

Objective:To investigate the mechanism of hypercholesterolemia with proatherosclersis,thrombosis and inflammation.We study the expression of CD40 ligand(CD40L)on platelets and soluble CD40L(sCD40L),and investigate whether them may be modified by statin therapy.Method:40 patients with hypercholesterolemia and 20 age sex-matched healthy control subjects were investigated.CD40L on platelets were detected by flow cytometry,sCD40L,serum monocyte chemoattractant protein-1(MCP-1)and prothrombin fragment F1+2 were measured by enzyme-linked immumosorbent assay(ELISA).Hypercholesterolemic patients were then randomized to either pravastatin 20 mg/d(n=20;group A)or diet(n=20;group B).The variables were measured at baseline and after 7 days of treatment.Results:patients with hypercholesterolemia showed a significant increase of platelet CD40L,sCD40L,serum MCP-1 and F1+2.sCD40L was significantly correlated with Platelet CD40L,TC,LDL,MCP-1 and F1+2.After 7days treatment showed a significantly decrease in platelet CD40L,sCD40L and MCP-1,F1+2 in group A,but no changes in group B.Conclusion:CD40L was significantly increased in hypercholesterolemic patients,proposed that activation of CD40L may create a proinflammatory and prothrombosis,developing atherosclerosis in hypercholesterolemia.Pravastatin therapy exerts a direct antiinflammatory and antirhrombotic effect via inhibition of platelet CD40L and CD40L mediated AS,independently of its cholesterole lowering effect.