Zhang Lin, Wu Yiling, Jia Zhenhua, Zhang Yun, Shen Hu Ying, Wang Xing Li
Michael E, DeBakey Department of Surgery, Baylor College of Medicine, Texas Heart Institute, Houston, Texas, USA.
BMC Complement Altern Med. 2008 Jul 14;8:39. doi: 10.1186/1472-6882-8-39.
Tong-Xin-Luo (TXL) - a mixture of herbal extracts, has been used in Chinese medicine with established therapeutic efficacy in patients with coronary artery disease.
We investigated the protective role of TXL extracts on endothelial cells injured by a known risk factor - palmitic acid (PA), which is elevated in metabolic syndrome and associated with cardiovascular complications. Human aortic endothelial cells (HAECs) were preconditioned with TXL extracts before exposed to PA for 24 hours.
We found that PA (0.5 mM) exposure induced 73% apoptosis in endothelial cells. However, when HAECs were preconditioned with ethanol extracted TXL (100 microg/ml), PA induced only 7% of the endothelial cells into apoptosis. Using antibody-based protein microarray, we found that TXL attenuated PA-induced activation of p38-MAPK stress pathway. To investigate the mechanisms involved in TXL's protective effects, we found that TXL reduced PA-induced intracellular oxidative stress. Through AMPK pathway, TXL restored the intracellular antioxidant system, which was depressed by the PA treatment, with an increased expression of thioredoxin and a decreased expression of the thioredoxin interacting protein.
In summary, our study demonstrates that TXL protects endothelial cells from PA-induced injury. This protection is likely mediated by boosting intracellular antioxidant capacity through AMPK pathway, which may account for the therapeutic efficacy in TXL-mediated cardiovascular protection.
通心络(TXL)——一种草药提取物混合物,在中国医学中已用于治疗冠状动脉疾病患者,疗效确切。
我们研究了通心络提取物对由已知危险因素——棕榈酸(PA)损伤的内皮细胞的保护作用,棕榈酸在代谢综合征中升高并与心血管并发症相关。人主动脉内皮细胞(HAECs)在暴露于PA 24小时之前先用通心络提取物预处理。
我们发现暴露于PA(0.5 mM)会诱导73%的内皮细胞凋亡。然而,当HAECs用乙醇提取的通心络(100微克/毫升)预处理时,PA仅诱导7%的内皮细胞凋亡。使用基于抗体的蛋白质微阵列,我们发现通心络减弱了PA诱导的p38-MAPK应激途径的激活。为了研究通心络保护作用的机制,我们发现通心络降低了PA诱导的细胞内氧化应激。通过AMPK途径,通心络恢复了被PA处理抑制的细胞内抗氧化系统,硫氧还蛋白表达增加,硫氧还蛋白相互作用蛋白表达减少。
总之,我们的研究表明通心络保护内皮细胞免受PA诱导的损伤。这种保护可能是通过AMPK途径增强细胞内抗氧化能力介导的,这可能解释了通心络介导的心血管保护的治疗效果。