氯沙坦對急性肺損傷/ 急性呼吸窘迫綜合征的治療作用_《中國呼吸與危重監護雜志》

作者：

沈利漢 ¹ , 莫紅纓 ² , 蔡立華 ¹ , 覃炳軍 ¹ , 肖正倫 ²

1 東莞市人民醫院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;

關鍵詞：

急性肺損傷/ 急性呼吸窘迫綜合征腎素-血管緊張素系統血管緊張素Ⅱ受體1拮抗劑氯沙坦

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目的研究腎素-血管緊張素系統( 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。方法采用盲腸結扎穿孔術( CLP) 復制小鼠ALI/ARDS模型, 術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, ALI/ARDS 小鼠的氧合指數和肺濕重/ 干重比( W/D) 顯示改善的趨勢; 但當氯沙坦的濃度超過15 mg/kg 時, 氧合指數和W/D 反而逐漸變差。氯沙坦( 15 mg/kg) 干預使小鼠血清中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) 。結論在一定劑量范圍內RAS 藥物氯沙坦可減輕CLP 誘導的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. 中國呼吸與危重監護雜志, 2010, 9(4): 409-412. doi: 復制

1.	沈利漢, 莫紅纓, 蔡立華, 等. 腎素-血管緊張素系統與ALI/ARDS 的關系探討. 中國呼吸與危重監護雜志, 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-血管緊張素系統與ALI/ARDS 的關系探討. 中國呼吸與危重監護雜志, 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.

《中國呼吸與危重監護雜志》

氯沙坦對急性肺損傷/ 急性呼吸窘迫綜合征的治療作用

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《中國呼吸與危重監護雜志》

氯沙坦對急性肺損傷/ 急性呼吸窘迫綜合征的治療作用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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