• 1 南華大學(xué)研究生院（湖南衡陽(yáng) 421001）;;
  • 2 湖南省老年醫(yī)院-老年醫(yī)學(xué)研究所呼吸疾病研究室（湖南長(zhǎng)沙 410016）;

目的 探討大鼠低氧性肺動(dòng)脈高壓( HPH) 形成過(guò)程中小泛素蛋白樣修飾蛋白1( SUMO-1) 在肺內(nèi)表達(dá)的動(dòng)態(tài)變化規(guī)律及在HPH 發(fā)病機(jī)制中的作用。方法 40 只Wistar 大鼠隨機(jī)
分為常氧對(duì)照組、低氧3 d 組、低氧7 d組、低氧14 d 組及低氧21 d 組, 每組8 只。常壓間斷低氧暴露復(fù)制HPH大鼠模型。檢測(cè)各組大鼠的平均肺動(dòng)脈壓( mPAP) 、右心室肥大指數(shù)( RVHI) 、血管形態(tài)學(xué)指標(biāo)[ 管壁面積/ 管總面積( WA%) ] ; 原位雜交、RT-PCR 檢測(cè)肺內(nèi)SUMO-1 mRNA 表達(dá), 免疫組化、Western blot 檢測(cè)其蛋白表達(dá)水平。結(jié)果 低氧7 d至21 d, 大鼠肺小動(dòng)脈開(kāi)始出現(xiàn)明顯血管重塑并逐漸加重, 低氧7 d 時(shí)WA% 和mPAP 顯著高于對(duì)照組; 低氧14 d 時(shí)WA% 、mPAP 較7 d 時(shí)進(jìn)一步增加, RVHI顯著高于對(duì)照組; 低氧21 d 時(shí)WA% 、RVHI 較14 d 時(shí)進(jìn)一步增加。SUMO-1 mRNA 和蛋白在對(duì)照組肺小動(dòng)脈壁呈弱陽(yáng)性表達(dá); 低氧3 d 后顯著增高; 低氧14 d 達(dá)高峰; 低氧21 d 后mRNA 表達(dá)
減弱但仍然高于對(duì)照組, 蛋白表達(dá)繼續(xù)保持高水平。SUMO-1 mRNA 和蛋白表達(dá)與mPAP、WA% 、RVHI 均呈正相關(guān)( P 均 lt;0. 01) 。結(jié)論 慢性低氧誘導(dǎo)肺內(nèi)SUMO-1 表達(dá)增加在HPH 的發(fā)病過(guò)程中發(fā)揮一定的作用。

引用本文： 田華,戴愛(ài)國(guó),符代炎,譚雙香,胡瑞成,朱黎明. 小泛素蛋白樣修飾蛋白1 在大鼠低氧性肺動(dòng)脈高壓發(fā)病中的作用. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2010, 9(1): 48-52. doi: 復(fù)制

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1. 田華,戴愛(ài)國(guó).HIF-1a可逆性SUMO化修飾.中國(guó)生物化學(xué)與分子生物學(xué)報(bào),2009,25:1-6.
2. Bohren KM,Nadkarni V,Song JH,et al.A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus.J Biol Chem,2004,279:27233-27238.
3. Shao R,Zhang FP,Tian F,et al.Increase of SUMO-1 expression in response to hypoxia: direct interaction with HIF-1alpha in adult mouse brain and heart in vivo.FEBS Lett,2004,569:293-300.
4. Carbia-Nagashima A,Gerez J,Perez-Castro C,et al.RSUME,a small RWD-containing protein,enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia.Cell,2007,131:309-323.
5. Bae SH,Jeong JW,Park JA,et al.Sumoylation increases HIF-1alpha stability and its transcriptional activity.Biochem Biophys Res Commun,2004,324:394-400.
6. 李熾觀,戴愛(ài)國(guó),嚴(yán)鵬科.低氧誘導(dǎo)因子1在低氧致肺動(dòng)脈平滑肌細(xì)胞增殖中的作用.中國(guó)病理生理雜志,2007,23: 1301-1305.
7. Li QF,Dai AG.Differential expression of three hypoxia-inducible factor-alpha subunits in pulmonary arteries of rat with hypoxia-induced hypertension.Acta Biochim Biophys Sin (Shanghai).2005,37:665-672.
8. Li QF,Dai AG.Hypoxia inducible factor-1 alpha correlates the expression of heme oxygenase 1 gene in pulmonary arteries of rat with hypoxia-induced pulmonary hypertension.Acta Biochim Biophys Sin (Shanghai),2004,36:133-140.
9. Li QF,Dai AG.Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.Chin Med J (Engl),2004,117:1023-1028.
10. Fu D,Dai A,Hu R,et al.Expression and role of factor inhibiting hypoxia-inducible factor-1 in pulmonary arteries of rat with hypoxia-induced hypertension.Acta Biochim Biophys Sin (Shanghai),2008,40:883-892.
11. Stenmark KR,Davie NJ,Reeves JT,et al.Hypoxia,leukocytes,and the pulmonary circulation.J Appl Physiol,2005,98:715-721.
  1. 1. 田華,戴愛(ài)國(guó).HIF-1a可逆性SUMO化修飾.中國(guó)生物化學(xué)與分子生物學(xué)報(bào),2009,25:1-6.
  2. 2. Bohren KM,Nadkarni V,Song JH,et al.A M55V polymorphism in a novel SUMO gene (SUMO-4) differentially activates heat shock transcription factors and is associated with susceptibility to type I diabetes mellitus.J Biol Chem,2004,279:27233-27238.
  3. 3. Shao R,Zhang FP,Tian F,et al.Increase of SUMO-1 expression in response to hypoxia: direct interaction with HIF-1alpha in adult mouse brain and heart in vivo.FEBS Lett,2004,569:293-300.
  4. 4. Carbia-Nagashima A,Gerez J,Perez-Castro C,et al.RSUME,a small RWD-containing protein,enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia.Cell,2007,131:309-323.
  5. 5. Bae SH,Jeong JW,Park JA,et al.Sumoylation increases HIF-1alpha stability and its transcriptional activity.Biochem Biophys Res Commun,2004,324:394-400.
  6. 6. 李熾觀,戴愛(ài)國(guó),嚴(yán)鵬科.低氧誘導(dǎo)因子1在低氧致肺動(dòng)脈平滑肌細(xì)胞增殖中的作用.中國(guó)病理生理雜志,2007,23: 1301-1305.
  7. 7. Li QF,Dai AG.Differential expression of three hypoxia-inducible factor-alpha subunits in pulmonary arteries of rat with hypoxia-induced hypertension.Acta Biochim Biophys Sin (Shanghai).2005,37:665-672.
  8. 8. Li QF,Dai AG.Hypoxia inducible factor-1 alpha correlates the expression of heme oxygenase 1 gene in pulmonary arteries of rat with hypoxia-induced pulmonary hypertension.Acta Biochim Biophys Sin (Shanghai),2004,36:133-140.
  9. 9. Li QF,Dai AG.Hypoxia-inducible factor-1 alpha regulates the role of vascular endothelial growth factor on pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.Chin Med J (Engl),2004,117:1023-1028.
  10. 10. Fu D,Dai A,Hu R,et al.Expression and role of factor inhibiting hypoxia-inducible factor-1 in pulmonary arteries of rat with hypoxia-induced hypertension.Acta Biochim Biophys Sin (Shanghai),2008,40:883-892.
  11. 11. Stenmark KR,Davie NJ,Reeves JT,et al.Hypoxia,leukocytes,and the pulmonary circulation.J Appl Physiol,2005,98:715-721.