羅非昔布調(diào)節(jié)血管內(nèi)皮生長(zhǎng)因子和誘導(dǎo)型一氧化氮合酶干預(yù)胃癌血管生成的實(shí)驗(yàn)研究.pdf

1、第二軍醫(yī)大學(xué)博士學(xué)位論文羅非昔布調(diào)節(jié)血管內(nèi)皮生長(zhǎng)因子和誘導(dǎo)型一氧化氮合酶干預(yù)胃癌血管生成的實(shí)驗(yàn)研究姓名：孫永強(qiáng)申請(qǐng)學(xué)位級(jí)別：博士專業(yè)：外科學(xué)（普外）指導(dǎo)教師：王強(qiáng)20050401羅非昔布調(diào)節(jié)血管內(nèi)皮生長(zhǎng)因子和誘導(dǎo)型一氧化氮合酶干預(yù)胃癌血管生成的實(shí)驗(yàn)研究【摘要】目的：探討環(huán)氧合酶一2抑制劑羅非昔布調(diào)節(jié)人胃癌SGC一7901裸鼠胃癌組織中血管內(nèi)皮生長(zhǎng)因子(vEGF)和誘導(dǎo)型一氧化氨合酶(州Os)的表達(dá)對(duì)胃癌血管生成的影響。方法：建立裸鼠入胃

2、癌原位種植轉(zhuǎn)移模型，用羅非昔布給裸鼠口服，觀察羅非昔布對(duì)原位種植瘤瘤重、抑瘤率及轉(zhuǎn)移的影響，同時(shí)通過免疫組化EnVision法及RTPCR檢測(cè)胃癌組織中的VEGF、INOS蛋白及VEGFmRNA、iNOSmRNA的表達(dá)，以觀察羅非昔布對(duì)VEGF、iNOS表達(dá)的影響。結(jié)果：成功地建立了裸鼠人胃癌原位種植轉(zhuǎn)移模型，移植瘤原位成瘤率100％：羅非昔布組的瘤重與對(duì)照組相比明顯縮小(PO05)，抑瘤率為41縱，肝轉(zhuǎn)移率及腹水形成率亦低于對(duì)照組。免

3、疫組化及RTPCR方法顯示，在蛋白及mRNA水平上，羅非昔布組VEGF、iNOS表達(dá)均明顯低于對(duì)照組(P005)。結(jié)論：羅非昔布可以通過降低腫瘤組織的VEGF、fNOS表達(dá)，使腫瘤血管生成受抑制，抑制胃癌細(xì)胞的增殖和轉(zhuǎn)移?！娟P(guān)鍵詞】羅非昔布胃癌環(huán)氧合酶一2抑制劑血管內(nèi)皮生長(zhǎng)因子誘導(dǎo)型一氧化氮合酶EnVision法逆轉(zhuǎn)錄聚合酶鏈反應(yīng)TheExperimentalStudyonRofecoxibSuppressingtheAngiogene

4、sisofGastricCarcinomabyRegulatingtheExpressionofVascularEndothelialGrowthFactorandInducibleNitricOxideSyuthase[Abstract]Objective：Tostudyoncyclooxyganase2inldbitorrofecoxibsuppressingtheangiogenesisofgastriccarcinomamode

5、lestablishedinnudemicebearinghumanSGC7901cellbyregulatingtheexpressionofvascularendothelialgrowthfactor(woF)andinduciblenitricoxidesynthase(iNOS)Methods：Toestablishthemodelsofhumangastriccarcinomainnudemicebyorthotopictr

6、ansplantationrofecoxibweietakenbynudemiceperdayThenthelocaltarBorweightinhibitaryrates，themetastasisofliverandesciticfluidformationwereevaluatedEnVisionirnmunohistochemicalstainingandRTPCRwereusedtodetecttheexpressionofV

7、EGF，iNOSatthelevelofproteinandmRNArespectivelyResults：ModelsofhumangastriccarcinomainnudemicebyorthotopictratlsplantatinnwasmadesuccessfulTheformationrateoftransplantedtunlourwas100％；Comparedwiththeweightoforthotopictunl

8、orincontrolgrouptumorweightinrofecoxibgroupweresignificantlyinhibited0005)Theinhibitoryrateoftnnlorwas412％InadditiontheincidencesoflivermetastasisandasciticfluidformationwerealsodecreasedintherofecoxibgroupExpressionofVE

9、GFandiNOSinmfecoxibgroupweresignificantlylowerthanthatofthecontrolgroupbyEnVisionirnmunobistochemicalandRTPCRmethod(p‘O05)Conclusions：Rofecor珂ocarlsignificantlyinhibitthegrowthandmetastasisoforthotopictransplantationgast

10、riccarcinomaofnudemicebydownregulatingtheexpressionofVEGFiNOSproteinandmRNAwhichsuppresstheangiogenesisofgastriccarcinomaKeywords：Rofccoxibgastriccarcinomacyclooxygenase2inhibitorVEGFiNOSEnVisionimmunohistochemicalmethod