羅非昔布調節(jié)血管內皮生長因子和誘導型一氧化氮合酶干預胃癌血管生成的實驗研究.pdf

1、第二軍醫(yī)大學博士學位論文羅非昔布調節(jié)血管內皮生長因子和誘導型一氧化氮合酶干預胃癌血管生成的實驗研究姓名：孫永強申請學位級別：博士專業(yè)：外科學（普外）指導教師：王強20050401羅非昔布調節(jié)血管內皮生長因子和誘導型一氧化氮合酶干預胃癌血管生成的實驗研究【摘要】目的：探討環(huán)氧合酶一2抑制劑羅非昔布調節(jié)人胃癌SGC一7901裸鼠胃癌組織中血管內皮生長因子(vEGF)和誘導型一氧化氨合酶(州Os)的表達對胃癌血管生成的影響。方法：建立裸鼠入胃

2、癌原位種植轉移模型，用羅非昔布給裸鼠口服，觀察羅非昔布對原位種植瘤瘤重、抑瘤率及轉移的影響，同時通過免疫組化EnVision法及RTPCR檢測胃癌組織中的VEGF、INOS蛋白及VEGFmRNA、iNOSmRNA的表達，以觀察羅非昔布對VEGF、iNOS表達的影響。結果：成功地建立了裸鼠人胃癌原位種植轉移模型，移植瘤原位成瘤率100％：羅非昔布組的瘤重與對照組相比明顯縮小(PO05)，抑瘤率為41縱，肝轉移率及腹水形成率亦低于對照組。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表達均明顯低于對照組(P005)。結論：羅非昔布可以通過降低腫瘤組織的VEGF、fNOS表達，使腫瘤血管生成受抑制，抑制胃癌細胞的增殖和轉移?！娟P鍵詞】羅非昔布胃癌環(huán)氧合酶一2抑制劑血管內皮生長因子誘導型一氧化氮合酶EnVision法逆轉錄聚合酶鏈反應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