辣椒素保護低密度脂蛋白及氧化型低密度脂蛋白所誘發內皮細胞損傷之作用機制研究

Protective Effects of Capsaicin against Low-Density Lipoprotein (LDL) Oxidation and Oxidized LDL-Induced Cytotoxicity on Endothelial Cells

李宜勳(Yi-Hsun, Lee)

指導教授 ： 謝易修 ； 陳霈霓

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2012年)

摘要

人體攝取過多的膽固醇，會導致血管中低密度脂蛋白(low-density lipoprotein; LDL)增加，過多的低密度脂蛋白(LDL)在動脈管壁上堆積，進而通過內皮細胞(endothelium cell)進入內皮層開始氧化作用形成氧化型低密度脂蛋白(oxidative modification of low-density lipoprotein;oxLDL)，過去文獻指出，氧化型低密度脂蛋白(oxLDL)在粥狀動脈硬化形成中扮演著重要的角色。辣椒素(Capsaicin)於辣椒中有很豐富的含量在日常生活中可輕易攝取，目前已知具有抗氧化(antioxidant) 抗發炎(anti-inflammation)等生物活性。在本篇文章中我們要探討辣椒素是否可以保護低密度脂蛋白免於氧化的壓力，形成氧化型低密度脂蛋白，抑制這種具有細胞毒性的氧化型低密度脂蛋白產生保護人類血管內皮細胞(HUVECs) ，是否可減少氧化型低密度脂蛋白產生而減少巨噬細胞吞噬氧化型低密度脂蛋白所產生的泡沫细胞(foam cells)。針對抑制LDL氧化實驗中，利用relative electrophoretic mobility (REM) shift assays、electrophoresis of ApoB fragmentation、lipid peroxidation assay，證實辣椒素可有效抑制硫酸銅所誘導LDL的氧化。在氧化型低密度脂蛋白對人類血管內皮細胞所造成的傷害實驗中，在辣椒素加藥處理作用下細胞凋亡的狀況於粒腺體膜電位測定(JC-1 stain)、細胞形態觀察及細胞凋亡檢測(DAPI stain)有明顯改善，在西方點墨法(Western blot)實驗中也有相同現象。根據以上實驗辣椒素具有抑制低密度脂蛋白的氧化和保護人類血管內皮細胞，且辣椒素可以減少氧化型低密度脂蛋白產生而減少巨噬細胞吞噬氧化型低密度脂蛋白所產生的泡沫细胞 (foam cells)。

關鍵字

辣椒素

並列摘要

Intake of too much cholesterol in the body, can cause the blood vessels in the LDL (low-density lipoprotein; LDL), increase, too much low-density lipoprotein accumulation in the arterial wall, and then enter through the endothelial cells cortex oxidation to the formation of oxidized low density lipoprotein (oxidative modification of low-density lipoprotein; oxLDL), past literature suggests that oxidized low-density lipoprotein (oxLDL), plays an important role in the development of atherosclerosis in the porridge status. Capsaicin chili in a very rich content in everyday life can easily uptake is known to have antioxidant biological activity of anti-inflammatory In this article we investigate the pressure of capsaicin can protect LDL from oxidation, the formation of oxidized low-density lipoprotein inhibit this cytotoxicity of oxidized low-density lipoprotein to produce a protective human vascular endothelial cells (HUVECs), can reduce oxidized low-density lipoprotein to produce reduced macrophage phagocytosis of foam cells by oxidized low density lipoprotein (foam cells). For the inhibition of LDL oxidation experiments, using relative by electrophoretic mobility (REM), the shift assays, electrophoresis was of of ApoB fragmentation is reported, the lipid peroxidation assay confirmed that capsaicin could effectively inhibit the sulfuric acid copper induced LDL oxidation. In the experiments of the damage caused by oxidized low-density lipoprotein on human endothelial cells, the apoptosis status of capsaicin-treatment under Determination of mitochondrial membrane potential in the particle (JC-1 stain), cell morphology and the detection of apoptosis (DAPI stain) has improved significantly, the same phenomenon in the Western blot experiments. Inhibition of LDL oxidation and protection of human vascular endothelial cells under the experimental capsaicin, and capsaicin can reduce oxidized low-density lipoprotein to produce reduced macrophage phagocytic foam cells in oxidized low density lipoprotein.

並列關鍵字

Capsaicin

參考文獻

Aoki, T., Abe, T., Yamada, E., Matsuto, T., and Okada, M. (2012). Increased LDL susceptibility to oxidation accelerates future carotid artery atherosclerosis. Lipids in health and disease 11, 4.

Attie, A.D., Pittman, R.C., and Steinberg, D. (1980). Metabolism of native and of lactosylated human low density lipoprotein: evidence for two pathways for catabolism of exogenous proteins in rat hepatocytes. Proceedings of the National Academy of Sciences of the United States of America 77, 5923-5927.

Bouguerne, B., Belkheiri, N., Bedos-Belval, F., Vindis, C., Uchida, K., Duran, H., Grazide, M.H., Baltas, M., Salvayre, R., and Negre-Salvayre, A. (2011). Antiatherogenic effect of bisvanillyl-hydralazone, a new hydralazine derivative with antioxidant, carbonyl scavenger, and antiapoptotic properties. Antioxidants & redox signaling 14, 2093-2106.

Duffin, R., Shaw, C.A., and Rossi, A.G. (2008). Sildenafil reduces alcohol-induced gastric damage: just say 'NO'. British journal of pharmacology 153, 623-624.

Finn, A.V., Nakano, M., Polavarapu, R., Karmali, V., Saeed, O., Zhao, X., Yazdani, S., Otsuka, F., Davis, T., Habib, A., et al. (2012). Hemoglobin directs macrophage differentiation and prevents foam cell formation in human atherosclerotic plaques. Journal of the American College of Cardiology 59, 166-177.