目的 研究腎素-血管緊張素系統(tǒng)( RAS) 藥物氯沙坦在急性肺損傷/ 急性呼吸窘迫綜合征( ALI/ARDS) 治療中的作用。方法 采用盲腸結(jié)扎穿孔術(shù)( CLP) 復(fù)制小鼠ALI/ARDS模型, 術(shù)后分別腹腔注射不同濃度氯沙坦( 5、10、15、20、25 mg/kg) , 研究氯沙坦對ALI/ARDS 小鼠肺損傷的影響, 并觀察氯沙坦作用后ALI/ARDS 小鼠7 d 生存率的變化。結(jié)果 氯沙坦顯著改善ALI/ARDS 小鼠肺損傷的程度, 在5 ～15 mg/kg 范圍內(nèi), ALI/ARDS 小鼠的氧合指數(shù)和肺濕重/ 干重比( W/D) 顯示改善的趨勢; 但當(dāng)氯沙坦的濃度超過15 mg/kg 時, 氧合指數(shù)和W/D 反而逐漸變差。氯沙坦( 15 mg/kg) 干預(yù)使小鼠血清中TNF-α[ ( 554. 1 ±62. 7) pg/mL 比( 759. 2 ±21. 5) pg/mL, P lt; 0. 01] 、IL-6[ ( 1227. 3 ±130. 0) pg/mL比( 2670. 4 ±174. 1) pg/mL, P lt;0. 01] 和IL-1β[ ( 444. 0 ±38. 6) p g/mL比( 486. 6 ±61. 7) pg/mL, P lt; 0. 05] 水平均顯著降低; 肺水腫明顯減輕; 小鼠7 d 生存率顯著提高( 6. 7% 比0) 。結(jié)論 在一定劑量范圍內(nèi)RAS 藥物氯沙坦可減輕CLP 誘導(dǎo)的ALI/ARDS 肺損傷, 提高ALI/ARDS小鼠7 d 生存率。
引用本文： 沈利漢,莫紅纓,蔡立華,覃炳軍,肖正倫. 氯沙坦對急性肺損傷/ 急性呼吸窘迫綜合征的治療作用. 中國呼吸與危重監(jiān)護雜志, 2010, 9(4): 409-412. doi: 復(fù)制
| 1. | 沈利漢, 莫紅纓, 蔡立華, 等. 腎素-血管緊張素系統(tǒng)與ALI/ARDS 的關(guān)系探討. 中國呼吸與危重監(jiān)護雜志, 2010, 9: 310 -314. |
| 2. | 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. |
| 3. | 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. |
| 4. | 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. |
| 5. | Jerng JS, Hsu YC, Wu HD, et al. Role of the renin-angiotensin system in ventilator-induced lung injury: an in vivo study in a rat model.Thorax, 2007, 62: 527-535. |
| 6. | Tsushima K, King LS, Aggarwal NR, et al. Acute lung injury review.Intern Med, 2009 , 48: 621-630. |
| 7. | Bedirli A, Kerem M, Pasaoglu H, et al. Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis. Shock, 2007, 27: 397-401 . |
| 8. | Meduri GU. Clinical review: a paradigm shift: the bidirectional effect of inflammation on bacterial growth. Clinical implications for patients with acute respiratory distress syndrome. Crit Care, 2002, 6: 24-29. |
| 9. | Yeh CC, Kao SJ, Lin CC, et al. The immunomodulation of endotoxininduced acute lung injury by hesperidin in vivo and in vitro. Life Sci,2007, 80: 1821-1831. |
- 1. 沈利漢, 莫紅纓, 蔡立華, 等. 腎素-血管緊張素系統(tǒng)與ALI/ARDS 的關(guān)系探討. 中國呼吸與危重監(jiān)護雜志, 2010, 9: 310 -314.
- 2. 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.
- 3. 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.
- 4. 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.
- 5. Jerng JS, Hsu YC, Wu HD, et al. Role of the renin-angiotensin system in ventilator-induced lung injury: an in vivo study in a rat model.Thorax, 2007, 62: 527-535.
- 6. Tsushima K, King LS, Aggarwal NR, et al. Acute lung injury review.Intern Med, 2009 , 48: 621-630.
- 7. Bedirli A, Kerem M, Pasaoglu H, et al. Beta-glucan attenuates inflammatory cytokine release and prevents acute lung injury in an experimental model of sepsis. Shock, 2007, 27: 397-401 .
- 8. Meduri GU. Clinical review: a paradigm shift: the bidirectional effect of inflammation on bacterial growth. Clinical implications for patients with acute respiratory distress syndrome. Crit Care, 2002, 6: 24-29.
- 9. Yeh CC, Kao SJ, Lin CC, et al. The immunomodulation of endotoxininduced acute lung injury by hesperidin in vivo and in vitro. Life Sci,2007, 80: 1821-1831.