砷形态对人脐静脉内皮细胞血管生成的影响及分子机制研究
发布时间:2018-06-20 05:43
本文选题:砷形态 + 人脐静脉内皮细胞 ; 参考:《暨南大学》2012年硕士论文
【摘要】:比较研究亚砷酸钠(NaAsO_2)、砷酸三钠(Na_3AsO_4)和洛克沙胂(Roxarsone)对人脐静脉内皮细胞(HUVEC)增殖、迁移及血管生成的影响,并重点分析亚砷酸钠对血管生成的调节作用及分子机制。 主要结果如下: 1、在HUVEC培养过程中,分别添加NaAsO_2(0-5μM)、Na_3AsO_4(0-40μM)和Roxarsone(0-80μM)处理48h,通过MTT检测法、流式细胞仪分析、划线实验及体外血管生成技术等检测手段分析三种不同砷形态对HUVEC增殖、周期、迁移及血管生成的影响。发现NaAsO_2浓度在0.25-1μM时,对HUVEC增殖及血管生成具有明显促进作用,而Na_3AsO_4和Roxarsone在实验剂量范围内,对HUVEC的增殖、迁移及血管生成的影响不明显。 2、进一步发现,添加0.25-1μM NaAsO_2处理HUVEC时,对细胞NO生成、NOS活性、Ca~(2+)流具有一定上调作用。当添加2.5-5μM的NaAsO_2时,则对NO生成和NOS活性具有下调作用。相应地,0.25-1μM的NaAsO_2对ROS具有下调作用,并可以明显的诱导HUVEC的体外血管生成,而2.5-5μM的NaAsO_2可以促进ROS的产生,,并对HUVEC的血管生成有明显的抑制作用。 综上所述,砷对HUVEC血管生成的影响与砷的形态有关,并呈现剂量依赖性及双重生物学效应。当低浓度时砷对血管生成具有促进作用,而高浓度时砷对此具有抑制作用。砷通过调节HUVEC中NO、NOS、ROS、Ca~(2+)等因子的含量,对信号通路产生调节作用,进而影响血管生成。
[Abstract]:The effects of sodium arsenite (NaAsO_2), sodium arsenate three (Na_3AsO_4) and Locke Shah (Roxarsone) on the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVEC) were compared, and the regulation and molecular mechanism of sodium arsenite on angiogenesis were emphatically analyzed.
The main results are as follows:
1, in the process of HUVEC culture, NaAsO_2 (0-5 M), Na_3AsO_4 (0-40 mu M) and Roxarsone (0-80 M) were used to treat 48h. The effects of three different arsenic forms on the proliferation, cycle, migration and angiogenesis of HUVEC were analyzed by MTT detection, flow cytometry, line test and angiogenesis in vitro. At 0.25-1 mu M, the proliferation and angiogenesis of HUVEC were significantly promoted, while the effects of Na_3AsO_4 and Roxarsone on the proliferation, migration and angiogenesis of HUVEC were not obvious within the experimental dose range.
2, it is further found that when adding 0.25-1 mu M NaAsO_2 to treat HUVEC, the NO generation, NOS activity and Ca~ (2+) flow have a certain up effect. 2.5-5 and M NaAsO_2 can promote the production of ROS and inhibit the angiogenesis of HUVEC.
As mentioned above, the effect of arsenic on the angiogenesis of HUVEC is related to the form of arsenic, and presents a dose-dependent and double biological effect. Arsenic has a promoting effect on angiogenesis at low concentration, while arsenic has a inhibitory effect at high concentration. Arsenic regulates the signaling pathway by regulating the content of NO, NOS, ROS, Ca~ (2+) and other factors in HUVEC. It affects angiogenesis.
【学位授予单位】:暨南大学
【学位级别】:硕士
【学位授予年份】:2012
【分类号】:R114
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