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

目的 探討大鼠低氧性肺動脈高壓( HPH) 形成過程中小泛素蛋白樣修飾蛋白1( SUMO-1) 在肺內表達的動態(tài)變化規(guī)律及在HPH 發(fā)病機制中的作用。方法 40 只Wistar 大鼠隨機
分為常氧對照組、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制HPH大鼠模型。檢測各組大鼠的平均肺動脈壓( mPAP) 、右心室肥大指數(shù)( RVHI) 、血管形態(tài)學指標[ 管壁面積/ 管總面積( WA%) ] ; 原位雜交、RT-PCR 檢測肺內SUMO-1 mRNA 表達, 免疫組化、Western blot 檢測其蛋白表達水平。結果 低氧7 d至21 d, 大鼠肺小動脈開始出現(xiàn)明顯血管重塑并逐漸加重, 低氧7 d 時WA% 和mPAP 顯著高于對照組; 低氧14 d 時WA% 、mPAP 較7 d 時進一步增加, RVHI顯著高于對照組; 低氧21 d 時WA% 、RVHI 較14 d 時進一步增加。SUMO-1 mRNA 和蛋白在對照組肺小動脈壁呈弱陽性表達; 低氧3 d 后顯著增高; 低氧14 d 達高峰; 低氧21 d 后mRNA 表達
減弱但仍然高于對照組, 蛋白表達繼續(xù)保持高水平。SUMO-1 mRNA 和蛋白表達與mPAP、WA% 、RVHI 均呈正相關( P 均 lt;0. 01) 。結論 慢性低氧誘導肺內SUMO-1 表達增加在HPH 的發(fā)病過程中發(fā)揮一定的作用。

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

1. 田華,戴愛國.HIF-1a可逆性SUMO化修飾.中國生物化學與分子生物學報,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,戴愛國,嚴鵬科.低氧誘導因子1在低氧致肺動脈平滑肌細胞增殖中的作用.中國病理生理雜志,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,戴愛國.HIF-1a可逆性SUMO化修飾.中國生物化學與分子生物學報,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,戴愛國,嚴鵬科.低氧誘導因子1在低氧致肺動脈平滑肌細胞增殖中的作用.中國病理生理雜志,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.