• 1 東莞市人民醫(yī)院ICU( 廣東東莞 523018) ;;
  • 2 廣州呼吸疾病研究所( 廣東廣州 510120)通訊作者: 沈利漢, E-mail: shenlihan@ hotmail. com;

目的  建立盲腸結(jié)扎穿孔術( CLP) 誘導的ALI/ARDS 動物模型, 研究ALI/ARDS 與腎素-血管緊張素系統(tǒng)( RAS) 的關系, 為ALI/ARDS 的治療探索新途徑。方法  在CLP 后18 h 觀察小鼠的癥狀、血氣分析、肺濕/ 干重比( W/D) 和肺組織病理等指標; 采用免疫組織化學、Western blot 和放射免疫等方法研究ALI/ARDS 動物模型中RAS 幾種關鍵酶( ACE、ACE2 和AngⅡ) 的變化規(guī)律, 應用卡托普利( ACE 拮抗劑) 、重組小鼠ACE2( rmACE2) 進行干預, 觀察干預后的變化。結(jié)果  CLP 誘導小鼠在術后18 h 出現(xiàn)典型的ALI/ARDS改變, 手術組較假手術組小鼠肺水含量明顯增多, PaO2 /FiO2明顯下降[ ( 194. 3 ±23. 9) mm Hg比( 346. 7 ±20. 5) mm Hg, P  lt;0. 01] , 肺組織病理出現(xiàn)明顯的肺損傷改變。Western blot 和免疫組化結(jié)果顯示: 與假手術組比較, ALI/ARDS 小鼠肺組織的ACE2 表達下降, ACE 無明顯差異。ALI/ARDS 小鼠機體的AngⅡ水平明顯升高; 藥物干預后, 與手術組比較, 卡托普利組和rmACE2 組不同程度的抑制體內(nèi)AngⅡ 的生成[ 肺: ( 1. 58 ±0. 16) fmol /mg、( 1. 65 ±0. 21) fmol /mg比( 2. 38 ±0. 41) fmol /mg; 血: ( 178. 04 ±17. 87) fmol /mL、( 153. 74 ±10. 24) fmol /mL比( 213. 38 ±25. 44) fmol /mL] 。結(jié)論  CLP誘導小鼠出現(xiàn)典型的ALI/ARDS 改變; ALI/ARDS 模型存在RAS 激活; ACE 對RAS 可能起正調(diào)節(jié)作用, ACE2 起負調(diào)節(jié)作用。

引用本文： 沈利漢 ,莫紅纓,蔡立華,覃炳軍,肖正倫. 腎素-血管緊張素系統(tǒng)與ALI /ARDS 的關系探討. 中國呼吸與危重監(jiān)護雜志, 2010, 9(3): 310-314. doi: 復制

1. Tsushima K, King LS, Aggarwal NR, et al. Acute lung injury review.Intern Med, 2009, 48: 621 -630.
2. 宋鵬, 李琦, 王長征, 等. 17 例重癥急性呼吸窘迫綜合征臨床資料回顧性分析. 中國呼吸與危重監(jiān)護雜志, 2006, 5: 35-38.
3. Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med, 2006 , 20: 1671-1684.
4. Orte C, Polak JM, Haworth SG, et al. Expression of pulmonary vascular angiotensin- converting enzyme in primary and secondary plexiform pulmonary hypertension. J Pathol, 2000, 192: 379 -384.
5. Otsuka M, Takahashi H, Shiratori M, et al. Reduction of bleomycin induced lung fibrosis by candesartan cilexetil, an angiotensin II type 1 receptor antagonist. Thorax, 2004, 59: 31-38.
6. 陸艷輝, 惠汝太, 趙彥芬, 等. ACE 基因插入/ 缺失多態(tài)與國人肺血栓栓塞癥的關聯(lián)研究. 中華結(jié)核和呼吸雜志, 2001 , 24: 265 -268.
7. Marshall RP, Webb S, Bellingan GJ, et al. Angiotensin converting enzyme insertion/ deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome.Am J Respir Crit Care Med, 2002, 166: 646 -650.
8. Li W, Moore MJ, Vasilieva N, et al. Angiotensin- converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 2003 ,426: 450-454.
9. Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects fromsevere acute lung failure. Nature, 2005, 436: 112-116 .
10. Imai Y, Kuba K, Penninger JM. Angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Cell Mol Life Sci, 2007, 64 :2006-2012.
11. Singleton KD, Beckey VE, Wischmeyer PE. Glutamine prevents activation of NF-KB and stress kinase pathways, attenuates inflammatory cytokine release, and prevents acute respiratory distress syndrome ( ARDS) following sepsis. Shock, 2005, 24: 583-589.
12. Weber KT. Fibrosis, a common pathway to organ failure: angiotensin II and tissue repair. Semin Nephrol, 1997 , 17: 467 -491.
13. Goss CH, Brower RG, Hudson LD, et al. Incidence of acute lung injury in the United States. Crit Care Med, 2003 , 31: 1607-1611.
14. Douglas GC, O′Bryan MK, Hedger MP, et al. The novel angiotensinconverting enzyme( ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology, 2004, 145: 4703 -4711.
15. Tipnis SR, Hooper NM, Hyde R, et al. A human homolog of angiotensin converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem, 2000 , 275 :33238 -33243.
16. Yamamoto T, Wang L, Shimakura K, et al. Angiotensin II-inducedpulmonary edema in a rabbit model. Jpn J Pharmacol, 1997 , 73: 33 -40.
17. Ruiz-Ortega M, Esteban V, Rupérez M, et al. Renal and vascular hypertension-induced inflammation: role of angiotensin II. Curr Opin Nephrol Hypertens, 2006, 15: 159 -166.
18. Filippatos G, Tilak M, Pinillos H, et al. Regulation of apoptosis by angiotension Ⅱ in the heart and lungs. Int J Mol Med, 2001, 7: 273 -280.
19. He X, Han B, Mura M, et al. Angiotensin-converting enzyme inhibitor captopril prevents oleic acid-induced severe acute lung injury in rats. Shock, 2007, 28: 106 -111.
  1. 1. Tsushima K, King LS, Aggarwal NR, et al. Acute lung injury review.Intern Med, 2009, 48: 621 -630.
  2. 2. 宋鵬, 李琦, 王長征, 等. 17 例重癥急性呼吸窘迫綜合征臨床資料回顧性分析. 中國呼吸與危重監(jiān)護雜志, 2006, 5: 35-38.
  3. 3. Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med, 2006 , 20: 1671-1684.
  4. 4. Orte C, Polak JM, Haworth SG, et al. Expression of pulmonary vascular angiotensin- converting enzyme in primary and secondary plexiform pulmonary hypertension. J Pathol, 2000, 192: 379 -384.
  5. 5. Otsuka M, Takahashi H, Shiratori M, et al. Reduction of bleomycin induced lung fibrosis by candesartan cilexetil, an angiotensin II type 1 receptor antagonist. Thorax, 2004, 59: 31-38.
  6. 6. 陸艷輝, 惠汝太, 趙彥芬, 等. ACE 基因插入/ 缺失多態(tài)與國人肺血栓栓塞癥的關聯(lián)研究. 中華結(jié)核和呼吸雜志, 2001 , 24: 265 -268.
  7. 7. Marshall RP, Webb S, Bellingan GJ, et al. Angiotensin converting enzyme insertion/ deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome.Am J Respir Crit Care Med, 2002, 166: 646 -650.
  8. 8. Li W, Moore MJ, Vasilieva N, et al. Angiotensin- converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 2003 ,426: 450-454.
  9. 9. Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects fromsevere acute lung failure. Nature, 2005, 436: 112-116 .
  10. 10. Imai Y, Kuba K, Penninger JM. Angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Cell Mol Life Sci, 2007, 64 :2006-2012.
  11. 11. Singleton KD, Beckey VE, Wischmeyer PE. Glutamine prevents activation of NF-KB and stress kinase pathways, attenuates inflammatory cytokine release, and prevents acute respiratory distress syndrome ( ARDS) following sepsis. Shock, 2005, 24: 583-589.
  12. 12. Weber KT. Fibrosis, a common pathway to organ failure: angiotensin II and tissue repair. Semin Nephrol, 1997 , 17: 467 -491.
  13. 13. Goss CH, Brower RG, Hudson LD, et al. Incidence of acute lung injury in the United States. Crit Care Med, 2003 , 31: 1607-1611.
  14. 14. Douglas GC, O′Bryan MK, Hedger MP, et al. The novel angiotensinconverting enzyme( ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology, 2004, 145: 4703 -4711.
  15. 15. Tipnis SR, Hooper NM, Hyde R, et al. A human homolog of angiotensin converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem, 2000 , 275 :33238 -33243.
  16. 16. Yamamoto T, Wang L, Shimakura K, et al. Angiotensin II-inducedpulmonary edema in a rabbit model. Jpn J Pharmacol, 1997 , 73: 33 -40.
  17. 17. Ruiz-Ortega M, Esteban V, Rupérez M, et al. Renal and vascular hypertension-induced inflammation: role of angiotensin II. Curr Opin Nephrol Hypertens, 2006, 15: 159 -166.
  18. 18. Filippatos G, Tilak M, Pinillos H, et al. Regulation of apoptosis by angiotension Ⅱ in the heart and lungs. Int J Mol Med, 2001, 7: 273 -280.
  19. 19. He X, Han B, Mura M, et al. Angiotensin-converting enzyme inhibitor captopril prevents oleic acid-induced severe acute lung injury in rats. Shock, 2007, 28: 106 -111.