中国临床药理学杂志
中國臨床藥理學雜誌
중국림상약이학잡지
The Chinese Journal of Clinical Pharmacology
2015年
18期
1849-1851
,共3页
肖顺武%张学军%代垠%犹春跃%谢明祥%王培%王玉玉%李毅
肖順武%張學軍%代垠%猶春躍%謝明祥%王培%王玉玉%李毅
초순무%장학군%대은%유춘약%사명상%왕배%왕옥옥%리의
硫化氢%神经胶质瘤%胱硫醚-β-合成酶%3-巯基丙酮酸硫转移酶%基质金属蛋白酶-9%缺氧诱导因子-1α
硫化氫%神經膠質瘤%胱硫醚-β-閤成酶%3-巰基丙酮痠硫轉移酶%基質金屬蛋白酶-9%缺氧誘導因子-1α
류화경%신경효질류%광류미-β-합성매%3-구기병동산류전이매%기질금속단백매-9%결양유도인자-1α
H2 S%glioblastoma%cystathionine -beta -synthase%3-mercaptopyruvate sulfurtransferase%matrix metallo proteinase-9%hypoxia-inducible transcription factors -1α
目的:研究外源性硫化氢( H2 S)对大鼠胶质瘤血管形成的诱导机制。方法成年SD大鼠40只,随机分为4组,对照组、硫氢化钠( NaHS)组、肿瘤组、肿瘤+NaHS组,每组10只。肿瘤组、肿瘤+NaHS组,大鼠纹状体内注射C6胶质瘤细胞,建立胶质瘤模型;对照组、NaHS组,大鼠大脑不做任何处理。4组大鼠正常饲养3周后,对其进行断头取脑,用敏感硫电极法检测各组大鼠脑组织及瘤内H2 S的含量;Real time PCR法检测胱硫醚-β-合成酶( CBS )、3-巯基丙酮酸硫转移酶(3-MST)的mRNA转录水平;ELISA及蛋白免疫印迹法检测缺氧诱导因子-1α( HIF -1α)、血管内皮生长因子( VEGF )、基质金属蛋白酶-9(MMP-9)的表达;同时计数瘤内微血管密度(CD105-MVD)。结果肿瘤组、肿瘤+NaHS组,均可见明显的肿瘤组织,与对照组相比,瘤内毛细血管数明显增多;肿瘤+NaHS组,瘤体内有更多的HIF-α、VEGF、MMP-9的表达,且MVD明显高于对照组、NaHS组、肿瘤组(均P<0.01)。结论外源性H2 S能诱导并促进大鼠恶性胶质瘤内的血管生成,其发生机制可能与H2 S促进CBS、3-MST、HIF-α、VEGF及MMP-9的表达密切相关。
目的:研究外源性硫化氫( H2 S)對大鼠膠質瘤血管形成的誘導機製。方法成年SD大鼠40隻,隨機分為4組,對照組、硫氫化鈉( NaHS)組、腫瘤組、腫瘤+NaHS組,每組10隻。腫瘤組、腫瘤+NaHS組,大鼠紋狀體內註射C6膠質瘤細胞,建立膠質瘤模型;對照組、NaHS組,大鼠大腦不做任何處理。4組大鼠正常飼養3週後,對其進行斷頭取腦,用敏感硫電極法檢測各組大鼠腦組織及瘤內H2 S的含量;Real time PCR法檢測胱硫醚-β-閤成酶( CBS )、3-巰基丙酮痠硫轉移酶(3-MST)的mRNA轉錄水平;ELISA及蛋白免疫印跡法檢測缺氧誘導因子-1α( HIF -1α)、血管內皮生長因子( VEGF )、基質金屬蛋白酶-9(MMP-9)的錶達;同時計數瘤內微血管密度(CD105-MVD)。結果腫瘤組、腫瘤+NaHS組,均可見明顯的腫瘤組織,與對照組相比,瘤內毛細血管數明顯增多;腫瘤+NaHS組,瘤體內有更多的HIF-α、VEGF、MMP-9的錶達,且MVD明顯高于對照組、NaHS組、腫瘤組(均P<0.01)。結論外源性H2 S能誘導併促進大鼠噁性膠質瘤內的血管生成,其髮生機製可能與H2 S促進CBS、3-MST、HIF-α、VEGF及MMP-9的錶達密切相關。
목적:연구외원성류화경( H2 S)대대서효질류혈관형성적유도궤제。방법성년SD대서40지,수궤분위4조,대조조、류경화납( NaHS)조、종류조、종류+NaHS조,매조10지。종류조、종류+NaHS조,대서문상체내주사C6효질류세포,건립효질류모형;대조조、NaHS조,대서대뇌불주임하처리。4조대서정상사양3주후,대기진행단두취뇌,용민감류전겁법검측각조대서뇌조직급류내H2 S적함량;Real time PCR법검측광류미-β-합성매( CBS )、3-구기병동산류전이매(3-MST)적mRNA전록수평;ELISA급단백면역인적법검측결양유도인자-1α( HIF -1α)、혈관내피생장인자( VEGF )、기질금속단백매-9(MMP-9)적표체;동시계수류내미혈관밀도(CD105-MVD)。결과종류조、종류+NaHS조,균가견명현적종류조직,여대조조상비,류내모세혈관수명현증다;종류+NaHS조,류체내유경다적HIF-α、VEGF、MMP-9적표체,차MVD명현고우대조조、NaHS조、종류조(균P<0.01)。결론외원성H2 S능유도병촉진대서악성효질류내적혈관생성,기발생궤제가능여H2 S촉진CBS、3-MST、HIF-α、VEGF급MMP-9적표체밀절상관。
Objective To study the mechanism induced by exogenous H2 S on rat glioma formation.Methods Fourty adult SD rats were ran-domly divided into control group , NaHS group , tumor group , tumor +NaHS group of four groups , each group 10.Tumor group , tumor+NaHS group injected rat striatum C 6 glioma cells to established glioma model . Control group, NaHS group received no treatment.Four groups of rats fed normally , three weeks after taking the brain sensitive sulfur electrode applied to detect the rat brain tumor and H 2 S content of its decapitated . The cystathionine -beta-synthase ( CBS ) , mRNA transcription level of 3-mercaptopyruvate sulfurtransferase (3MST) were determined by real time PCR assay. The hypoxia -inducible transcription factors -1α(HIF-1α), vascular endothelial growth factor (VEGF) and the expre-ssion of matrix metallo proteinase-9 ( MMP-9 ) by ELISA and Western blot.The intratumoral micro vessel density ( MVD ) was counted by CD105 -MVD. Results Compared with the control group , NaHS group, tumor group, tumor +NaHS group were clearly visible tumor tissue, significantly increased the number of tumor capillaries .Tumor+NaHS group has more CBS , 3MST, HIF-α, VEGF expression of MMP -9.And tumor +NaHS group was significantly higher than the NaHS group , tumor group ( P<0.01 ) .Conclusion Exogenous H 2 S may induce and promote angiogenesis in rat glioma within its mechanism of H2S promote CBS, 3MST, closely related to the HIF-αVEGF expression of matrix metalloproteinase MMP -9.