氧化低密度脂蛋白致血管平滑肌细胞损伤和阿司匹林的干预

The Role and Mechamism of Aspirin in Injury of Vascular SmoothMuscle Cells by Oxidized Low Density Lipoprotein

目的 :探讨阿司匹林 (aspirin)对氧化低密度脂蛋白 (oxLDL)致血管平滑肌细胞 (VSMC)损伤的保护作用及其机制。方法 :硝酸酶还原法测定VSMC培养液中一氧化氮 (NO)水平 ;MTT比色法测VSMC增殖活度 ;比色底物法检测VSMC培养液中的组织纤溶酶原激活剂 (t PA)和纤溶酶原激活剂抑制剂 1(PAI 1)的活性。结果 :5 0mg·L- 1 的oxLDL作用 2 4h可使VSMC培养液NO水平由 (82 .0 4± 7.89) μmol·L- 1 降低到 (4 8.11± 6 .4 3) μmol·L- 1 ,并明显刺激VSMC增殖 ,使其增殖活度 (MTT OD值 )明显高于对照组 (P <0 .0 5 ) ;同时培养液中PAI 1活性显著升高 ,t PA活性显著降低。治疗剂量 (3,6mmol·L- 1 )Aspirin可显著提高VSMC培养液中NO水平 ,明显抑制oxLDL对VSMC增殖的刺激作用 ,并显著降低培养液中PAI 1活性 ,升高t PA活性。结论 :Aspirin能抑制oxLDL刺激的VSMC增殖 。

Objective: To explore the role and mechamism of Aspirin in injury of vascular smooth muscle cells(VSMC) by oxidized low density lipoprotein(oxLDL). Methods: The method of cellular culture,MTT colorimetric assay was performed for the effect of oxLDL on proliferation of cultured human umbilical arterial smooth muscle cells and Aspirin treatment. The dysfunction of VSMC was determined by measuring tissue plasminogen activator(t PA) and plasminogen activator inhibitor 1(PAI 1) activity with Chromogenix. The nitric oxide (NO) level was measured by Enzyme method. Results: VSMC exposed to oxLDL(50 mg·L -1 ) could stimulate the proliferation of VSMC and increased PAI 1 activity 1.6 times more than control per 24 h per 5×10 4 cells (P<0.05),decreased t PA activity and VSMC NO production(P<0.01). But Aspirin interfered with oxLDL stimulating effects on VSMC, Aspirin(3～5 mmol·L -1 ) caused a significant decrease in MTT OD values and PAI 1 activity (P<0.05) and increased t PA activity and NO production. Conclusion: Spirin could significantly inhibit the proliferation of VSMC exposed to oxLDL in vitro and increase VSMC NO production.