BACKGROUND:Hepatic hypoxia-inducible factor-1(HIF-1) is activated in the progression of hepatocellular carcinoma (HCC).This study aimed to investigate the dynamic alterations of HIF-1αand its gene expression so as to...BACKGROUND:Hepatic hypoxia-inducible factor-1(HIF-1) is activated in the progression of hepatocellular carcinoma (HCC).This study aimed to investigate the dynamic alterations of HIF-1αand its gene expression so as to explore the relationship between HIF-1αexpression and hepatocarcinogenesis at the early stage of HCC. METHODS:A hepatoma model was made with 2-fluorenyl- acetamide(2-FAA)in male Sprague-Dawley rats.Morphological changes of rat hepatocytes were assessed pathologically (HE staining).The dynamic expression of hepatic and circulating HIF-1αwas quantitatively analyzed by ELISA. The gene fragments of hepatic HIF-1αmRNA were amplified by RT-PCR and confirmed by sequencing.The cellular distribution of hepatic HIF-1αexpression was confirmed by immunohistochemistry. RESULTS:Histological examination confirmed granulelike degeneration to atypical hyperplasia and HCC development in rat hepatocytes and progressive increases in the levels of hepatic and circulating HIF-1αand its gene expression during the course.The levels of HIF-1α expression in the liver and blood of rats with hepatoma were significantly higher than those in normal ratsand those with degeneration.Immunohistochemical analysis confirmed the positive expression and hepatocyte distribution of HIF-1αin the development of rat hepatoma. A positive relationship was found between HIF-1α expression in the liver and blood(P<0.01). CONCLUSIONS:The above observations support the hypothesis that the overexpression of HIF-1αand its gene are closely associated with the malignant transformation of hepatocytes and play an important role at the stage of hepatocarcinogenesis.展开更多
目的:观察慢性萎缩性胃炎(CAG)大鼠胃黏膜淤血与缺氧诱导因子(HIF)-1α、血管内皮生长因子(VEGF)表达的关系,以及穴位埋线对两者的影响,探讨穴位埋线改善CAG的机制。方法:将健康成年雄性SD大鼠分为空白组10只、模型组9只和埋线组10只。...目的:观察慢性萎缩性胃炎(CAG)大鼠胃黏膜淤血与缺氧诱导因子(HIF)-1α、血管内皮生长因子(VEGF)表达的关系,以及穴位埋线对两者的影响,探讨穴位埋线改善CAG的机制。方法:将健康成年雄性SD大鼠分为空白组10只、模型组9只和埋线组10只。采用自由饮用100μg/mL N-甲基-N’-硝基-N-亚硝基胍溶液配合饥饱失常法制备CAG大鼠模型。埋线组大鼠予"中脘"及双侧"足三里""脾俞"穴埋线治疗,10 d 1次,共治疗6次。采用HE染色法观察各组大鼠胃黏膜病理情况,采用Western blot法检测各组大鼠胃黏膜HIF-1α、VEGF蛋白表达水平。结果:HE染色显示,空白组大鼠胃黏膜结构清晰,胃腺丰富;模型组大鼠黏膜固有层局部腺体发生萎缩、减少和变性坏死,部分伴有黏膜淤血;埋线组可见部分胃黏膜上皮细胞脱落、胞质淡染,腺体扩张、坏死。与空白组相比,模型组腺体坏死、萎缩与黏膜淤血大鼠数量显著增多(P<0.001,P<0.05);与模型组相比,埋线组腺体坏死、萎缩与黏膜淤血大鼠数量显著减少(P<0.01,P<0.05)。模型组共有5只大鼠存在胃黏膜淤血情况,设为淤血组,另4只设为非淤血组;与淤血组相比,非淤血组胃黏膜HIF-1α、VEGF蛋白表达降低(P<0.01)。与空白组相比,模型组胃黏膜HIF-1α、VEGF蛋白表达升高(P<0.01);与模型组相比,埋线组胃黏膜HIF-1α、VEGF蛋白表达降低(P<0.05,P<0.01)。结论:胃黏膜淤血与HIF-1α、VEGF蛋白的异常表达密切相关,穴位埋线可能通过降低HIF-1α、VEGF蛋白表达,从而发挥治疗CAG的作用。展开更多
基金supported by grants-in-aid from the 333 Project(No.2007099)Project of the Health Department,Jiangsu Province,China(H200523)
文摘BACKGROUND:Hepatic hypoxia-inducible factor-1(HIF-1) is activated in the progression of hepatocellular carcinoma (HCC).This study aimed to investigate the dynamic alterations of HIF-1αand its gene expression so as to explore the relationship between HIF-1αexpression and hepatocarcinogenesis at the early stage of HCC. METHODS:A hepatoma model was made with 2-fluorenyl- acetamide(2-FAA)in male Sprague-Dawley rats.Morphological changes of rat hepatocytes were assessed pathologically (HE staining).The dynamic expression of hepatic and circulating HIF-1αwas quantitatively analyzed by ELISA. The gene fragments of hepatic HIF-1αmRNA were amplified by RT-PCR and confirmed by sequencing.The cellular distribution of hepatic HIF-1αexpression was confirmed by immunohistochemistry. RESULTS:Histological examination confirmed granulelike degeneration to atypical hyperplasia and HCC development in rat hepatocytes and progressive increases in the levels of hepatic and circulating HIF-1αand its gene expression during the course.The levels of HIF-1α expression in the liver and blood of rats with hepatoma were significantly higher than those in normal ratsand those with degeneration.Immunohistochemical analysis confirmed the positive expression and hepatocyte distribution of HIF-1αin the development of rat hepatoma. A positive relationship was found between HIF-1α expression in the liver and blood(P<0.01). CONCLUSIONS:The above observations support the hypothesis that the overexpression of HIF-1αand its gene are closely associated with the malignant transformation of hepatocytes and play an important role at the stage of hepatocarcinogenesis.
文摘目的:观察慢性萎缩性胃炎(CAG)大鼠胃黏膜淤血与缺氧诱导因子(HIF)-1α、血管内皮生长因子(VEGF)表达的关系,以及穴位埋线对两者的影响,探讨穴位埋线改善CAG的机制。方法:将健康成年雄性SD大鼠分为空白组10只、模型组9只和埋线组10只。采用自由饮用100μg/mL N-甲基-N’-硝基-N-亚硝基胍溶液配合饥饱失常法制备CAG大鼠模型。埋线组大鼠予"中脘"及双侧"足三里""脾俞"穴埋线治疗,10 d 1次,共治疗6次。采用HE染色法观察各组大鼠胃黏膜病理情况,采用Western blot法检测各组大鼠胃黏膜HIF-1α、VEGF蛋白表达水平。结果:HE染色显示,空白组大鼠胃黏膜结构清晰,胃腺丰富;模型组大鼠黏膜固有层局部腺体发生萎缩、减少和变性坏死,部分伴有黏膜淤血;埋线组可见部分胃黏膜上皮细胞脱落、胞质淡染,腺体扩张、坏死。与空白组相比,模型组腺体坏死、萎缩与黏膜淤血大鼠数量显著增多(P<0.001,P<0.05);与模型组相比,埋线组腺体坏死、萎缩与黏膜淤血大鼠数量显著减少(P<0.01,P<0.05)。模型组共有5只大鼠存在胃黏膜淤血情况,设为淤血组,另4只设为非淤血组;与淤血组相比,非淤血组胃黏膜HIF-1α、VEGF蛋白表达降低(P<0.01)。与空白组相比,模型组胃黏膜HIF-1α、VEGF蛋白表达升高(P<0.01);与模型组相比,埋线组胃黏膜HIF-1α、VEGF蛋白表达降低(P<0.05,P<0.01)。结论:胃黏膜淤血与HIF-1α、VEGF蛋白的异常表达密切相关,穴位埋线可能通过降低HIF-1α、VEGF蛋白表达,从而发挥治疗CAG的作用。
