中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
CHINESE JOURNAL OF ONCOLOGY
2012年
4期
254-258
,共5页
李战永%刘仕昌%许蓬娟%杨卓%张涛
李戰永%劉仕昌%許蓬娟%楊卓%張濤
리전영%류사창%허봉연%양탁%장도
神经胶质瘤%硫化氢%新生血管形成%缺氧诱导因子1,α亚基%CD34%大鼠
神經膠質瘤%硫化氫%新生血管形成%缺氧誘導因子1,α亞基%CD34%大鼠
신경효질류%류화경%신생혈관형성%결양유도인자1,α아기%CD34%대서
Glioma%Hydrogen sulfide%Angiogenesis%Hypoxia-inducible factor 1,alpha subunit%CD34%Rats
目的 探讨硫化氢(H2S)在大鼠恶性胶质瘤生长中的作用及其机制.方法 将40只雄性成年SD大鼠随机分为对照组、硫氢化钠(NaHS)组、肿瘤组、肿瘤+NaHS组,每组10只.对照组脑内注射人工脑脊液1周后,腹腔注射生理盐水；NaHS组脑内注射人工脑脊液1周后,腹腔注射NaHS溶液；肿瘤组脑内注射C6细胞悬液1周后,腹腔注射生理盐水；肿瘤+NaHS组脑内注射C6细胞1周后,腹腔注射NaHS.每组大鼠均正常饲养3周,观察记录大鼠的一般状况和体重增长情况.处死大鼠,测定大鼠脑组织中H2S的含量,组织病理学检查瘤体细胞形态变化并测量瘤体体积,免疫组化法检测缺氧诱导因子1α(HIF-1α)和CD34的表达以及瘤内微血管密度(MVD).结果 与对照组相比,NaHS组各项指标无显著变化；肿瘤组大鼠一般状况明显较差,体重增加缓慢；肿瘤+NaHS组大鼠机体消耗症状明显加重,部分大鼠体重出现负增长.肿瘤组大鼠瘤体体积为( 32.0±6.9)mm3,肿瘤+ NaHS组为(67.8±11.9) mm3,NaHS处理后的大鼠瘤体体积显著增大(P ＜0.001).与肿瘤组相比,肿瘤+ NaHS组大鼠肿瘤组织中HIF-1α和CD34表达量均显著增加.肿瘤组和肿瘤+NaHS组大鼠肿瘤组织中MVD分别为(41.2 ±7.9)/mm2和(97.0±10.8)/mm2,差异有统计学意义(P＜0.001).对照组、NaHS组、肿瘤组、肿瘤+NaHS组大鼠脑内H2S含量分别为(29.12 ±0.94)nmol/g、( 29.73±0.76) nmol/g、( 35.25±1.03) nmol/g和(40.81±1.21) nmol/g.统计分析显示,对照组和NaHS组H2S含量差异无统计学意义(P＞0.05),肿瘤组H2S含量显著高于对照组(P＜0.05),肿瘤+ NaHS组含量显著高于肿瘤组(P＜0.05).结论 恶性胶质瘤的生长伴随内源性H2S含量的增加,外源性H2S能促进恶性胶质瘤的生长,其机制与H2S促进肿瘤细胞增殖和瘤内新生血管形成有关.
目的 探討硫化氫(H2S)在大鼠噁性膠質瘤生長中的作用及其機製.方法 將40隻雄性成年SD大鼠隨機分為對照組、硫氫化鈉(NaHS)組、腫瘤組、腫瘤+NaHS組,每組10隻.對照組腦內註射人工腦脊液1週後,腹腔註射生理鹽水；NaHS組腦內註射人工腦脊液1週後,腹腔註射NaHS溶液；腫瘤組腦內註射C6細胞懸液1週後,腹腔註射生理鹽水；腫瘤+NaHS組腦內註射C6細胞1週後,腹腔註射NaHS.每組大鼠均正常飼養3週,觀察記錄大鼠的一般狀況和體重增長情況.處死大鼠,測定大鼠腦組織中H2S的含量,組織病理學檢查瘤體細胞形態變化併測量瘤體體積,免疫組化法檢測缺氧誘導因子1α(HIF-1α)和CD34的錶達以及瘤內微血管密度(MVD).結果 與對照組相比,NaHS組各項指標無顯著變化；腫瘤組大鼠一般狀況明顯較差,體重增加緩慢；腫瘤+NaHS組大鼠機體消耗癥狀明顯加重,部分大鼠體重齣現負增長.腫瘤組大鼠瘤體體積為( 32.0±6.9)mm3,腫瘤+ NaHS組為(67.8±11.9) mm3,NaHS處理後的大鼠瘤體體積顯著增大(P ＜0.001).與腫瘤組相比,腫瘤+ NaHS組大鼠腫瘤組織中HIF-1α和CD34錶達量均顯著增加.腫瘤組和腫瘤+NaHS組大鼠腫瘤組織中MVD分彆為(41.2 ±7.9)/mm2和(97.0±10.8)/mm2,差異有統計學意義(P＜0.001).對照組、NaHS組、腫瘤組、腫瘤+NaHS組大鼠腦內H2S含量分彆為(29.12 ±0.94)nmol/g、( 29.73±0.76) nmol/g、( 35.25±1.03) nmol/g和(40.81±1.21) nmol/g.統計分析顯示,對照組和NaHS組H2S含量差異無統計學意義(P＞0.05),腫瘤組H2S含量顯著高于對照組(P＜0.05),腫瘤+ NaHS組含量顯著高于腫瘤組(P＜0.05).結論 噁性膠質瘤的生長伴隨內源性H2S含量的增加,外源性H2S能促進噁性膠質瘤的生長,其機製與H2S促進腫瘤細胞增殖和瘤內新生血管形成有關.
목적 탐토류화경(H2S)재대서악성효질류생장중적작용급기궤제.방법 장40지웅성성년SD대서수궤분위대조조、류경화납(NaHS)조、종류조、종류+NaHS조,매조10지.대조조뇌내주사인공뇌척액1주후,복강주사생리염수；NaHS조뇌내주사인공뇌척액1주후,복강주사NaHS용액；종류조뇌내주사C6세포현액1주후,복강주사생리염수；종류+NaHS조뇌내주사C6세포1주후,복강주사NaHS.매조대서균정상사양3주,관찰기록대서적일반상황화체중증장정황.처사대서,측정대서뇌조직중H2S적함량,조직병이학검사류체세포형태변화병측량류체체적,면역조화법검측결양유도인자1α(HIF-1α)화CD34적표체이급류내미혈관밀도(MVD).결과 여대조조상비,NaHS조각항지표무현저변화；종류조대서일반상황명현교차,체중증가완만；종류+NaHS조대서궤체소모증상명현가중,부분대서체중출현부증장.종류조대서류체체적위( 32.0±6.9)mm3,종류+ NaHS조위(67.8±11.9) mm3,NaHS처리후적대서류체체적현저증대(P ＜0.001).여종류조상비,종류+ NaHS조대서종류조직중HIF-1α화CD34표체량균현저증가.종류조화종류+NaHS조대서종류조직중MVD분별위(41.2 ±7.9)/mm2화(97.0±10.8)/mm2,차이유통계학의의(P＜0.001).대조조、NaHS조、종류조、종류+NaHS조대서뇌내H2S함량분별위(29.12 ±0.94)nmol/g、( 29.73±0.76) nmol/g、( 35.25±1.03) nmol/g화(40.81±1.21) nmol/g.통계분석현시,대조조화NaHS조H2S함량차이무통계학의의(P＞0.05),종류조H2S함량현저고우대조조(P＜0.05),종류+ NaHS조함량현저고우종류조(P＜0.05).결론 악성효질류적생장반수내원성H2S함량적증가,외원성H2S능촉진악성효질류적생장,기궤제여H2S촉진종류세포증식화류내신생혈관형성유관.
Objective To address the hypothesis that hydrogen sulfide (H2S) is a functionally significant stimulator in the development of glioblastoma (GBM) and explore the mechanism of stimulation.Methods Forty adult Sprague-Dawley (SD) rats were given intracerebral injection of rat C6 glioma cell suspension,and an intraperitoneal injection of sodium hydrosulfide (NaHS),an exogenous H2S donor.The 40 rats were randomly divided into 4 groups of 10 rats in each:the control group,NaHS group,C6 glioma group (intracerebral implantation of C6 glioma cells) and C6-NaHS group (intracerebral implantation of C6 glioma cells and intraperitoneal injection of NaHS).Food and water were freely available during all phases of the experiment.Physical symptoms were observed and the tumor size was measured.Histological changes were examined by pathology.Immunohistochemical staining was used to analyze the expression of HIF-1 α and integrated optical density (IOD) was used to determine the tumor microvessel density (MVD).The H2S content in the brain was measured.Results The physical symptoms of tumor-bearing rats became more serious after NaHS injection.The H2S level in the C6 glioma group was higher than that in the control group [ (35.25 ± 1.03 ) nmol/g vs.(29.12 ± 0.94) nmol/g,P ＜ 0.05 ],and the highest H2S level was found in the C6-NaHS group.The pathological examination showed that the implanted tumors were predominantly spheroid with a distinct border and no capsule could be detected. Neovascular proliferation was also observed.Foci of tumor necrosis,intratumoral hemorrhage,pseudopalisades and tumor cavity were clearly observed.The glioma cells had scant eosinophilic cytoplasm and enlarged hyperchromatic nuclei.All these phenomena were more markedly in the C6-NaHS group compared with that in other three groups.The mean tumor volume was significantly different between the C6 and C6-NaHS rats [ (32.0 ± 6.9) mm3 vs.(67.8 ± 11.9) mm3,P ＜ 0.001 ].Immunohistochemical analysis exhibited that the hypoxia-inducible factor-1alpha (HIF-1α) and CD34 expression were significantly increased after the intraperitoneal injection of NaHS in the C6-NaHS rats (comparing the IOD between C6-NaHS group and C6 group,HIF-1α:133 962.9 ±451.4 vs.38 569.8 ± 408.6,P ＜ 0.001 ; CD34:73 368.6 ± 404.8 vs.14 570.6 ± 748.7,P ＜ 0.001 ).Moreover,compared with the C6 group,there were higher MVD in the C6-NaHS group [ (41.2 ± 7.9)/mm2 vs.(97.0 ±10.8)/mm2,P ＜0.001 ].Conclusions H2S serves as a stimulator in the development of rat glioblastoma and exogenous H2S strongly promotes the tumor growth.The stimulating mechanisms include the increase of HIF-1α expression and neovascular formation. H2S may be a significant regulator in the development of tumor.
