UM E-Theses Collection (澳門大學電子學位論文庫)
- Title
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The proangiogenic effect of saponins from Panax notoginseng in human umbilical vein endothelial cells (HUVEC)
- English Abstract
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Angiogenesis plays an important pathological role in a wide range of diseases, such as cancer (Folkman J, et al., 1999; Amano.M et al., 2007), various ischemic and inflammatory diseases. (Carmeliet P, et al., 2000; József TÍMÁR et al., 2001). Substantial studies have showed that researches on angiogenic effects of Chinese medicine leads to discovery of many active pro-angiogenic and anti-angiogenic compounds and novel mechanism of angiogensis (Fan T.P, et al., 2006). Panax notoginseng, as a commonly used "blood circulation promoting" herb in traditional Chinese medicine, is a potential candidate for the purpose. 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. Panax notoginseng, commonly used in the prescriptions of traditional Chinese medicine for blood circulation promotion and to be a potential candidate for the disease cure. However, the biological effects of saponin extract from Panax notoginseng (PNS) on angiogenesis and the underlying mechanisms are yet to be fully elucidated. This investigation describes the angiogenic effects of PNS, ginsenoside Rgi, ginsenoside Re and notoginsenoside R1 on HUVEC in vitro. The extract and three monomers were identified to stimulate the proliferation of HUVEC by XTT assay and microscopic cell counting. A significant increase in numbers of invaded cells was observed in PNS and the monomers treated HUVEC using the invasion assay. In addition, we observed a significant increase in number of branch points during endothelial cell capillary formation after treatments with either PNS or the monomer. Moreover, PNS was found to enhance VEGF, KDR/Flk-1 and FIt-1 mRNA expression by real-time PCR and the PNS induced-HUVEC proliferation could be abolished by a KDR/Flk-1 inhibitor. Furthermore, the proliferations of HUVEC induced by PNS and the monomers were significantly abrogated by inhibitors of PI3K, Akt and eNOS. All results suggest that saponin extract (PNS) and its' constituents (Rgl, Re and R1) isolated from Panax notoginseng can promote angiogenesis in multiple models, and the pro-angiogenic effects involve VEGF-KDR/FIk-1 and PI3K-Akt-eNOS dependent signaling pathways.
- Chinese Abstract
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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不衡的功能。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,腫瘤租織中不斷有新生血管生成,這些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,如類風澡關節炎、眼底病、銀脣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冶療是有益的,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。 三七为五加科 (Araliaceae)植物三七Panax notoginseng (Burk)F.H. Chen.的乾燥根 是我國名貴的活血化淤类中藥。其中,三七总皂音为其作用的主要成分。 但是,关于三七总皂苷怎樣作用於血管新生還沒有清晰的解說。此外,RI作为三七特有的皂苷类单体,在血管新生方面未见报道。因此,本文將以人臍靜脉內皮細胞(HUVEC)作體外模型描述三七总皂苷及其三醇型主要了个单体R1, Rgl 和 Re 是如何影響血管新生。首先,以XTT和細胞計數的方法確定是否能刺激HUVEC 增值。再檢測H!PNS, R1, Rgl 和Re 可增加細胞的侵人數目和形成管结的数目。另外,在real-time PCR檢測中,加有PNS的HUVEC內VEGF的mRNA表達也有增量;进一步用细胞通路抑制剂来进一步证明作用的途径。
- Issue date
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2007.
- Author
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Hong, Si Jia
- Faculty
- Institute of Chinese Medical Sciences
- Degree
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M.Sc.
- Subject
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Materia medica -- Therapeutic use
Materia medica, Vegetable -- China -- Analysis
- Supervisor
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Lee, Ming-Yuen
- Files In This Item
- Location
- 1/F Zone C
- Library URL
- 991000542549706306