论文部分内容阅读
目的考察木樨草素对溶血性磷脂酰胆碱(LPC)所引起的大鼠主动脉内膜依赖性舒张(EDR)紊乱的改善作用,并通过人脐静脉内皮细胞的研究,进一步探讨了其对内膜的化学保护作用和相关机制。方法制备大鼠内膜完整的主动脉环,苯肾上腺素预收缩,给予LPC刺激,观察其对EDR的影响。MTT测定细胞增殖,RT-PCR检测内皮型一氧化氮合酶(eNOS)、诱导型一氧化氮合酶(iNOS)、环氧合酶(COX)-1和COX-2的mRNA的表达,Western blot法检测细胞外信号调节蛋白激酶(ERK)磷酸化改变。结果 LPC刺激使血管对乙酰胆碱所引起的EDR显著下降。木樨草素通过对内膜源性舒张因子和超极化因子的调节表现出对抗LPC的作用,改善乙酰胆碱引起动脉环的EDR,并呈浓度依赖性;ERK的特异性抑制剂PD98059亦表现出相同的作用。LPC低浓度(<20μmol·L~(-1))对内皮细胞表现出细胞增殖作用,高浓度则呈细胞毒性作用,而木樨草素对LPC引起的细胞增殖和细胞毒性均表现出有效的对抗作用。木樨草素和PD98059上调LPC抑制的eNOS和COX-1 mRNA表达,同时对LPC所引起的iNOS和COX-2mRNA表达表现出有效的抑制作用。木樨草素亦有效抑制了LPC所引起的ERK1/2磷酸化活化。结论在大鼠离体动脉环上,木樨草素对抗LPC,通过抑制炎症反应而呈现出血管内膜完整性的保护作用,有效改善了受损的血管内膜依赖性舒张的生物活性。木樨草素改善血管内膜功能紊乱对其在防治心血管疾病方面的应用具有一定的积极意义。
Objective To investigate the effect of luteolin on the improvement of rat aortic intima-dependent relaxation (EDR) caused by hemolytic phosphatidylcholine (LPC), and further explore its effect on human umbilical vein endothelial cells. Intimal chemical protection and related mechanisms. Methods The intact aortic rings of rat intima were prepared and phenylephrine was precontracted and stimulated by LPC to observe its effect on EDR. MTT was used to measure cell proliferation. RT-PCR was used to detect the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-1 and COX-2 mRNA. The phosphorylation of extracellular signal-regulated protein kinase (ERK) was detected by blotting. Results LPC stimulation significantly reduced the EDR caused by acetylcholine in blood vessels. Hypoxycortin exerts an anti-LPC effect on the regulation of endothelium-derived relaxing factor and hyperpolarizing factor, improves the EDR of arterial rings caused by acetylcholine in a concentration-dependent manner, and PD98059, an ERK-specific inhibitor, also shows the same effect. The role. Low concentration of LPC (<20 μmol·L -1 ) showed cell proliferation in endothelial cells and cytotoxicity in high concentration, but luteolin had an effective countermeasure against LPC-induced cell proliferation and cytotoxicity. effect. The luteolin and PD98059 up-regulated the expression of eNOS and COX-1 mRNA inhibited by LPC, and showed effective inhibition on the expression of iNOS and COX-2 mRNA induced by LPC. The luteolin also effectively inhibited the activation of ERK1/2 phosphorylation by LPC. CONCLUSION: On rat isolated arterial rings, luteolin challenged LPC and inhibited the inflammatory response to show a protective effect on the intimal integrity of the blood vessels, effectively improving the invasive biological activity of the damaged intima. The use of luteolin to improve the intimal function of blood vessels has a certain positive significance in the application of prevention and treatment of cardiovascular diseases.