UM E-Theses Collection (澳門大學電子學位論文庫)
- Title
-
The proangiogenic effect of Radix Astragali extract and astragaloside IV in human umbilical vein endothelial cells (HUVEC)
- English Abstract
-
Show / Hidden
Angiogenesis, the formation of new blood vessels, is essential for normal growth and homeostasis in human body. However, certain diseases can be exacerbated by the loss of balance in angiogenesis, which results in either excessive or insufficient blood vessel formation. Diseases such as cancer, diabetic retinopathy and rheumatoid arthritis are characterized by excessive blood vessel formation while peripheral and coronary ischemia and infarction, chronic wound healing failure and ulcers are characterized by insufficient blood vessel formation. Radix Astragali, named huangqi in Chinese, is commonly used in the prescriptions of traditional Chinese medicine. In traditional systems, it is used to replenish the vital energy for the treatment of lacking strength, anorexia and loose stools, prolapse of uterus and anus, spontaneous sweating, and chronic nephritis with edema and proteinuria, and to dispel pus and accelerate the healing of chronic ulcers. The saponin astragaloside IV (AS-IV; Fig.1), a 3-0-6-Dxylopyranosyl-6-O-B-D-glucopyranosylcycloastragenol was purified from the Chinese medical herb Astragalus membranaceus (Fisch) Bge, is regarded as a characteristic and active constituent of Radix Astragali and the content of astragaloside IV is the main criterion of its quality assurance and control.. Recently, Radix Astragali and astragaloside IV were proved to be a potential candidate to cure the diseases, driven by imbalanced angiogenesis. However, the biological effects of Radix Astragali and astragaloside IV on angiogenesis and the underlying mechanisms are unclear yet. This investigation describes the angiogenic effects of Radix Astragali extract and astragaloside IV on HUVEC in vitro. The extract and its' constituent marker was identified to stimulate the proliferation of HUVEC by XTT assay and microscopic cell counting. The wound healing migration assay illustrated that the dramatic increment of migration could be measured in Radix Astragali extract and astragaloside IV treated HUVEC. Meanwhile, the numbers of invaded cells and the number of branching points were significantly increased in both treatment groups. In addition, Radix Astragali extract and astragaloside IV was found to enhance VEG mRNA expression by real-time PCR, and a VEGF receptor specific blocker, SU5416, could inhibit Radix Astragali extract- and astragaloside IV - induced HUVEC proliferation. Furthermore, the stimulation of HUVEC cell proliferation by 12.5 pg/ml Radix Astragali extract and 100 g/ml astragaloside IV could be blocked by the phosphatidylinositol 3-kinase (PI3K), Akt and endothelial nitric oxide synthase (eNOS) inhibitor (wortmannin, SH-6, L-NAME) respectively. All results suggest that Radix Astragali extract and astragaloside IV can promote angiogenesis in multiple models and probably through VEGF-VEGF tyrosine kinase receptor and PI3K-Akt-eNOS,
- Chinese Abstract
-
Show / Hidden
血管新生 (angiogenesis),是指形成新血管的過程,具有維持人體正常的生長和本衡的功能。在許多疾病的發生、發展及轉歸、預後中扮演著重要的角色。 近年來,調節血管新生的研究已成爲臨床治療中的熱點。研究主要集中在兩個方面:1.許多疾病的發生、發展與血管生成有著密切的關係,如惡性腫瘤在其生長 過程中,腫瘤組織中不斷有新生血管生成,這此新生血管爲腫瘤的生長提供了豐富的供血和營養。同時,由於新生血管管壁較薄,腫瘤細胞易於穿過,從而進入血循環並發生遠處轉移。因此,如能抑制新生血管的生成,也就可以阻斷腫瘤供血,達到“餓死”癌細胞的目的。其他一些良性疾病,如頻風瀑關節炎、眼底病、 銀屑病等也與局部血管過度增生有關。2.促進血管生成對許多疾病的治療是有益的,對於骨折、創傷患者,如能促進創傷局部的血管生成,就可以改善局部供血,加快癒合。又如心肌梗塞患者,梗塞部位新生血管的生成對恢復受損心肌組織供血有重要意義。 近來,黄芪及其有效成分黄芪甲苷己被證明具有治療由不規則血管新生所引起的病症的能力。但是,黄芪及其有效成分怎樣作用於血管新生還沒有清晰的解說。因此,本文將以人臍靜脈内皮細胞(HUVEC)作體外模型描述當歸提取物是如何影響血管新生。首先,以XTT和細胞計數的方法確定黄芪提取物黄芪甲苷能刺激HUVEC增值。在wounding healing遷移測試方法中,檢測出黃芪提取物組及黃芪甲苷組具有顯著的遷移現象。同時,也檢測出黃芪提取物及黄芪甲苷可增加細胞的侵入數目和管形交叉點。另外,在real-time PCR檢測中,加有黃芪提取物及 黃芪甲苷的HUVEC内VEGF的mRNA表達也有增量,而且加入KDR/FIK-1/VEGFR -2抑制劑後,黄芪提取物組及黄芪甲苷組中HUVEC的增殖被完全阻斷。易外,黃芪提取物組及黃芪甲苷組HUVEC的增殖能被PI3K、Alt、eNOS的阻斷劑所抑制。所有檢測結果都表明黄芪提取物及黄芪甲苷能夠提高血管新生的能力。
- Issue date
-
2007.
- Author
-
Zhang, Yi
- Faculty
- Institute of Chinese Medical Sciences
- Degree
-
M.Sc.
- Subject
-
Astragalus (Plants)
Materia medica -- China
- Supervisor
-
Lee, Ming-Yuen
- Files In This Item
- Location
- 1/F Zone C
- Library URL
- 991000542149706306