https://scholars.lib.ntu.edu.tw/handle/123456789/192104
標題: | Captopril 及Iosartan 對大鼠原位肝細胞癌血管新生之影響 The effect of Captopril and Iosar tan on Angiogenesis of Rat Orthotopic Hepatocellular Carcinoma |
作者: | 袁瑞晃 | 關鍵字: | 大鼠肝細胞癌;血管新生;血管內 皮細胞生長因子;鹼性纖維母細胞生長因 子;微小血管密度;Iosartan;Captopril;Rat hepatocellular carcinoma;Angiogenesis;Vascular endothelial growth factor;Basic fibroblast growth factor;microvessel density | 公開日期: | 31-七月-2000 | 出版社: | 臺北市:國立臺灣大學醫學院外科 | 摘要: | 在許多腫瘤的研究中發現,血管新 生現象和腫瘤的形成及進展密不可分, 最近也有許多血管新生的研究特別重視 它和癌症細胞轉移的關係,因而抑制腫 瘤血管新生對於腫瘤的治療是一個新的 方向。目前對於肝細胞癌血管新生的研 究報告大多在於分析腫瘤細胞株在動物 皮下組織分泌血管生成因子的能力或利 用人類肝細胞腫瘤組織回溯性地研究血 管生成因子在腫瘤形成過程中所扮演的 角色,而針對原位性肝細胞癌血管新生 抑制因子前溯性的研究則付之闕如。 Captopril 為血管增壓素轉換脢抑制 劑,可以減少血管增壓素II 的形成,常 用於高血壓的控制,目前有研究發現其 可以抑制血管內皮細胞DNA 的合成進 而抑制血管新生的現象,然而其血管新 生抑制機制是否經由抑制血管增壓素轉 換脢而作用,或是經由另一新的途徑則 值得研究。Iosartan 也用於高血壓的調 控,為血管增壓素II 受器的拮抗劑,可 以減少血管增壓素II 的作用,此藥物是 否如同Captopril 有新生血管抑制作用, 間接證明血管增壓素II 是否為血管新生 途徑之一也是值得研究的。 本實驗的特性在於其前瞻性,in vivo study,利用大鼠肝細胞癌細胞株GP7TB, 先注入老鼠的皮下約二三週等到腫瘤形 成,再將腫瘤切除並切成約一立方毫米之 腫瘤塊,並將此小腫瘤塊利用手術方式植 入同種老鼠的肝臟中,做出活體原位肝細 胞腫瘤的動物模式,並將此老鼠分成對照 組、Captopril (CA)組(餵食60 mg/kg/day 之Captopril)及Iosartan (I)組(餵食20 mg/kg/day 之Iosartan)三組。在植入腫瘤 後十四及二十一天取出肝臟,測量腫瘤大 小、重量,並且分別定量血管內皮細胞生 長因子(vascular endothelial growth factor)、鹼性纖維母細胞生長因子(Basic fibroblast growth factor)及其mRNA expression 能力,以檢驗Captopril 以及 Iosartan 對於原位肝細胞癌血管生成抑制 作用的程度以及差別,並探討其中機制的 異同。 The assessment of angiogenesis provides a promising horizon in the pathogenesis of a variety of cancer diseases. Recent studies of angiogenesis demonstrated an important role of angiogenesis in cancer growth and metastasis. In the mean time, inhibition of angiogenesis might provide a new approach in cancer treatment. Reports concerning angiogenesis of hepatocellular carcinoma were restricted to either secretion function of angiogenic factors in cell lines or to histochemical studies on human hepatocellular carcinoma tissue retrospectively at present. Unfortunately, a prospective study of anti-angiogenesis in an orthotopic hepatocellular carcinoma in rat is not present. Captopril is an inhibitor of angiotensin converting enzyme, which can reduce the production of angiotensin II, and is widely used clinically in the management of hypertesive disease. Inhibition of DNA production in endothelial cells by captopril resulted in decreasing of angiogenesis had been reported recently. But further researches are demanded to study the mechanism. Iosartan, a new developed drug for hypertension treatment, is an antagonist of angiotensin II subtype I receptor with competitive inhibition of angiotensin II. It's worth to understand the effect of drug in order to clarify the role of angiotensin II in angiogenesis. In this study, we use the chemical carcinogen transformed hepatic epithelial cancer cell line, GP7TB to establish an orthotopic hepatocellular carcinoma model for in vivo study. GP7TB cell suspension is inoculated subcutaneous in the posterior flanks of the rats. Two to three weeks later, tumor formed at subcutaneous region will be excised and cut into uniform fragments of about 1 mm3. Then the fragment is transplanted into the liver of syngeneic Fischer 334 rats. The rats will be divided into 3 groups. In Control (C) group, only normal saline was given, In Captopril (CA) group, 60 mg/kg/day of Captopril will be given. In Iosartan (I) group, 20 mg/kg/day of Iosartan will be given. After 14 and 21 days, the rats will be sacrificed and the size, weight of the tumor will be recorded. In addition, quantification of angiogenic factors including vascular epithelial growth factor, and basic fibroblast growth factor as well as ability of mRNA expression will be done at the same time. The differences of anti-angiogenic ability and mechanism between Captopril and Iosartan will be discussed. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/24422 | 其他識別: | 892314B002220 | Rights: | 國立臺灣大學醫學院外科 |
顯示於: | 醫學系 |
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