砷形態(tài)對(duì)人臍靜脈內(nèi)皮細(xì)胞血管生成的影響及分子機(jī)制研究
發(fā)布時(shí)間:2018-06-20 05:43
本文選題:砷形態(tài) + 人臍靜脈內(nèi)皮細(xì)胞 ; 參考:《暨南大學(xué)》2012年碩士論文
【摘要】:比較研究亞砷酸鈉(NaAsO_2)、砷酸三鈉(Na_3AsO_4)和洛克沙胂(Roxarsone)對(duì)人臍靜脈內(nèi)皮細(xì)胞(HUVEC)增殖、遷移及血管生成的影響,并重點(diǎn)分析亞砷酸鈉對(duì)血管生成的調(diào)節(jié)作用及分子機(jī)制。 主要結(jié)果如下: 1、在HUVEC培養(yǎng)過(guò)程中,分別添加NaAsO_2(0-5μM)、Na_3AsO_4(0-40μM)和Roxarsone(0-80μM)處理48h,通過(guò)MTT檢測(cè)法、流式細(xì)胞儀分析、劃線實(shí)驗(yàn)及體外血管生成技術(shù)等檢測(cè)手段分析三種不同砷形態(tài)對(duì)HUVEC增殖、周期、遷移及血管生成的影響。發(fā)現(xiàn)NaAsO_2濃度在0.25-1μM時(shí),對(duì)HUVEC增殖及血管生成具有明顯促進(jìn)作用,而Na_3AsO_4和Roxarsone在實(shí)驗(yàn)劑量范圍內(nèi),對(duì)HUVEC的增殖、遷移及血管生成的影響不明顯。 2、進(jìn)一步發(fā)現(xiàn),添加0.25-1μM NaAsO_2處理HUVEC時(shí),對(duì)細(xì)胞NO生成、NOS活性、Ca~(2+)流具有一定上調(diào)作用。當(dāng)添加2.5-5μM的NaAsO_2時(shí),則對(duì)NO生成和NOS活性具有下調(diào)作用。相應(yīng)地,0.25-1μM的NaAsO_2對(duì)ROS具有下調(diào)作用,并可以明顯的誘導(dǎo)HUVEC的體外血管生成,而2.5-5μM的NaAsO_2可以促進(jìn)ROS的產(chǎn)生,,并對(duì)HUVEC的血管生成有明顯的抑制作用。 綜上所述,砷對(duì)HUVEC血管生成的影響與砷的形態(tài)有關(guān),并呈現(xiàn)劑量依賴性及雙重生物學(xué)效應(yīng)。當(dāng)?shù)蜐舛葧r(shí)砷對(duì)血管生成具有促進(jìn)作用,而高濃度時(shí)砷對(duì)此具有抑制作用。砷通過(guò)調(diào)節(jié)HUVEC中NO、NOS、ROS、Ca~(2+)等因子的含量,對(duì)信號(hào)通路產(chǎn)生調(diào)節(jié)作用,進(jìn)而影響血管生成。
[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.
【學(xué)位授予單位】:暨南大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2012
【分類號(hào)】:R114
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