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低氧诱导因子-1α和内皮素-1基因在大鼠低氧性肺动脉高压中的表达 被引量:21

Expression of hypoxia-inducible factor-1 alpha and endothelin-1 gene in hypoxic pulmonary hypertension
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摘要 目的 探讨低氧诱导因子 1(HIF 1α)和内皮素 1(ET 1)基因表达在低氧性肺动脉高压发病过程中的变化和作用。方法 复制低氧性肺动脉高压大鼠模型 ,测定平均肺动脉压 ,弹力纤维染色显示腺泡内肺动脉 ,用放射免疫法测ET含量 ,原位杂交方法进行检测HIF 1αmRNA。结果 HIF 1αmRNA在低氧各组腺泡内肺动脉有表达 ,低氧 14d组 (0 2 5 6 9± 0 0 46 8)和低氧 2 8d组 (0 2 2 5 8±0 0 45 3)染色强于低氧 5d组 (0 145 5± 0 0 2 72 )和正常组 (0 110 9± 0 0 2 2 4) ;ET 1mRNA在低氧各组腺泡内肺动脉有表达 ,低氧 14d组 (0 412 2± 0 0 783)和低氧 2 8d组 (0 36 84± 0 0 72 9)染色强于低氧5d组 (0 2 0 17± 0 0 34 9)和正常组 (0 185 5± 0 0 36 1) ,HIF 1α和ET 1基因表达在H14d组和H2 8d组明显增加 (P <0 0 5 )。肺动脉血中ET 1含量在H14d组 [(15 8 78± 2 5 14)pg/ml]和H2 8d组 [(142 93± 2 3 38)pg/ml]明显高于H5d组 [(79 6 8± 12 5 4)pg/ml]和正常组 [(6 5 37± 10 82 )pg/ml](P <0 0 5 ) ;H14d组 [(34 0± 5 8)mmHg]和H2 8d组 [(2 9 0± 4 7)mmHg]的mPAP也明显高于H5d组[(19 0± 3 5 )mmHg]和正常组 [(17 0± 2 8)mmHg](P <0 .0 5 ) ,并且与肺动脉血中ET Objective To investigate the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and endothelin-1 (ET-1) gene in hypoxic pulmonary hypertension (HPH). Methods The animal model of HPH was replicated. The elastic fiber staining was applied to show the intraacinar pulmonary artery (IAPA). Radioimmunoassay (RIA) and in situ hybridization (ISH) were used for detection of HIF-1a and . ET-1. Results ISH showed that HIF-1α mRNA was expressed in the IAPA of all hypoxic rat. The expression was stronger in the H14 d (0.256 9±0.046 8) and H28 d (0.225 8±0.045 3) groups than in the H5 d (0.1455±0.072 2) and control (0.110 9±0.022 4) groups ( P <0.05), the expression of ET-1 mRNA in the H14 d (0.412 2± 0.078 3) and H28 d (0.368 4±0.072 9) groups was also stronger than that in the H5 d (0.201 7±0.034 9) and control (0.185 5±0.036 1) groups ( P <0.05). The amount of ET-1 in pulmonary arteial blood in the H14 d [(158.78±25.14) pg/ml] and H28 d [(142.93±23.38) pg/ml] groups was significantly higher than that in the H5 d [(79.68±12.54) pg/ml] and control [(65.37±10.82) pg/ml] groups ( P <0.05). The mean pulmonary arterial pressure (mPAP) in the H14 d [(34.0±5.8) mm Hg] and H 28 d[(29.0±4.7) mm Hg] groups was markedly higher than that in the H5 d [(19.0±3.5) mm Hg] and control [(17.0±2.8) mm Hg] groups ( P <0.05). A positive rank correlation existed between the mPAP and the amount of ET-1 ( rs =0.747, P <0.05). Conclusions Expression of HIF-1α and ET-1 mRNA in IAPA increase under long-term hypoxic condition and both show consistent expression, indicating that the expression of HIF-1a and ET-1 gene contribute to pathogenesis of HPH.
出处 《中华病理学杂志》 CAS CSCD 北大核心 2002年第2期140-142,共3页 Chinese Journal of Pathology
基金 国家自然科学基金资助项目 ( 39730 190 )
关键词 大鼠 低氧诱导因子-1Α 内皮素-1 低氧性肺动脉高压 基因表达 Hypoxia-inducible factor-1 alpha Endothelin-1 Hypoxic pulmonary hypertension
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