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UM E-Theses Collection (澳門大學電子學位論文庫)

Title

The inhibitory effect of l-tetrahydropalmatine (l-THP) on TNF-alpha-induced adhesion molecule expression in human endothelial cells

English Abstract

Atherosclerosis (AS) is a variety of cardiovascular and cerebrovascular diseases pathophysiological basis, mainly involving large and medium-sized arteries which can lead to heart, brain, and other organs and tissues ischemic necrosis, myocardial infarction, and brain death and so on. The pathogenesis of atherosclerosis involves a complex series of events, similar to a chronic inflammatory process, with the formation of atherosclerotic plaque as the end result. Corydalis yanhusuo also called Rhizoma corydalis is well known as a traditional Chinese herbal medicine, prepared from the dried tubers of Corydalis yanhusuo W.T. Wang, It has gained ever-increasing popularity in today's world because of its therapeutic effects for promoting blood circulation, reinforcing vital energy and alleviating pain such as headache, chest pain, epigastric pain, abdominal pain, backache, arthralgia or trauma. The chemical constituents of Corydalis yanhusuo W.T. Wang have been investigated in some detail like tertiary and quaternary alkaloids, including dehydrocorydaline (DHC), Berberine corydaline, tetrahydropalmatine (THP), protopine, Boldine, palmatine, tetrahydrocoptisine, tetrahydrocolumbamine and corybulbine. And /-THP is regarded as a characteristic and active constituent of Corydalis yanhusuo W.T. Wang and the content of 1-THP is the main criterion of its quality assurance and control.. /-THP was demonstrated as a very effective monoamine depletory in the brain that has excellent neuroprotective effects such as analgesic, sedative and hypnotic actions. Recently, l-THP was proved to be a potential candidate to cure the diseases, such as anti-arrhythmic, anti-hypertensive and prevention of ischaemic-reperfusion injury. However, the biological effects of /-THP on Atherosclerosis and the underlying mechanisms are unclear yet. This investigation describes the protective effects of /-THP of AS on HUVEC in vitro. l-THP could deceased the adhesion of THP-1cell and HUVECs, 30 micromolar of /-THP-treatment inhibited the TNF-a induced expression of VCAM-1 and ICAM-1 by western blotting, Flow and ELISA assay. Immunostaining assay show that 1-THP could regulated NF-kB translocation. Furthermore. /-THP was found to decreased ICAM-1 and VCAM-1 mRNA expression by real-time PCR, Our results suggest that /-THP inhibits the expression of molecules involved in the inflammatory process, therefore it could be used as an alternative in the treatment of chronic inflammatory diseases such as atherosclerosis. Key words: Atherosclerosis, /-THP, adhesion, HUVECs

Chinese Abstract

摘要 动脉粥样硬化(Atherosclerosis)所致的心、脑血管疾病是目前人类死亡的主要 原因之一。动脉粥样硬化由多因素引起,其发病机理到目前为止仍未完全确定, 而脂代谢异常和局部血管的炎症反应均参与了动脉粥样硬化的形成。在动脉粥样 硬化的发生发展过程中,会出现多种细胞因子、炎症分子、脂质和纤维成分的增 加,当它们的数量积聚到一定程度时,即会出现临床心、脑血管病事件。在以前的 研究中已经注意到细胞粘附分子(cell adhesion molecules, CAMs)在动脉粥样 硬化斑块中的表达水平和动脉粥样硬化的发生发展过程相一致,并认为它们在动 脉粥样硬化性疾病的发病机制中起重要作用. 延胡索乙素系粟科紫革属植物延胡索(Corydalis yanhusuoW. T. Wang) 根茎中的主要有效成分,又称左旋四氢巴马汀(-tetrahydropalmatine, FTHP)。 药理研究认为,延胡索乙素有效部分为左旋体,其药理作用与阻滞中枢多巴胺 (DA)受体有关,目前作为镇痛药应用于临床。除具有镇痛、镇静、催眠等作用外, 还有降压和抗心律失常作用,近几年来,许多研究表明1-THP具有抗脑缺血效应。 但是对于左旋延四氢巴马汀抗动脉粥样硬化及其机制的研究鲜有报道,因此,本 文將以人臍靜脈內皮細胞(HUVECs)作體外模型描述左旋延四氢巴马汀是如何抗 动脉粥样硬化的。首先,用MTT法选取可用的浓度最高为30uM,在与THP-1细胞的 黏附实验中,I-THP可以明显降低THP-1细胞与HUVEC的黏附率,在测定HUVEC细胞 的黏附分子的ELISA, FLOW, Immunostaining和IWB实验中,F-THP可以明显抑制 ICAM-1和VCAM-1的表达;另外,在real-time PCR檢測中,加入I-THP再用TNF-a 刺激后VCAM-1和ICAM-1也有不同程度的降低;同时,1-THP可以调节NF-KB的信号 传导通路。所有这些结果提示I-THP具有抗动脉粥样硬化的作用。 关键词:动脉粥样硬化,左旋四氢巴马汀,人臍靜脈內皮細胞

Issue date

2008.

Author

Yu, Nan

Faculty
Institute of Chinese Medical Sciences
Degree

M.Sc.

Subject

Arteriosclerosis

Herbs -- Therapeutic use

Supervisor

Lee, Ming-Yuen

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Location
1/F Zone C
Library URL
991005252539706306