目的 觀察胸部開放傷海水浸泡致ALI 早期血管內(nèi)皮生長(zhǎng)因子( VEGF) 及其可溶性受體sVEGFR-1 在血漿、BALF 和肺組織的水平變化, 探討VEGF 表達(dá)在胸部開放傷海水浸泡致ALI 發(fā)病機(jī)制中的作用。方法 16 只成年雜交犬隨機(jī)分為對(duì)照組( 單純胸部開放傷) 和海水組( 胸部開放傷海水浸泡致ALI) 。于胸部開放傷后0、2、4、6 及8 h, 監(jiān)測(cè)生命體征并取動(dòng)、靜脈血。測(cè)定各時(shí)相點(diǎn)外周血白細(xì)胞計(jì)數(shù)( WBC) 、血?dú)狻㈦娊赓|(zhì)和血漿滲透壓, 采用ELISA 法檢測(cè)血漿IL-1β和IL-8 水平, 血管性血友病因子( vWF) 水平, VEGF及受體sVEGFR-1 水平。8 h取BALF 和肺組織, HE 染色觀察肺組織病理改變, ELISA 法檢測(cè)BALF 及肺組織勻漿中VEGF 及受體sVEGFR-1 水平。測(cè)定傷后8 h BALF 和血漿中蛋白含量, 并計(jì)算肺泡通透指數(shù)( BALF中蛋白含量/ 血漿蛋白含量) 。結(jié)果 與對(duì)照組比較, 海水組肺組織病理切片見毛細(xì)血管擴(kuò)張淤血嚴(yán)重, 肺間質(zhì)和肺泡腔內(nèi)有大量水腫液積聚, 部分肺泡結(jié)構(gòu)的完整性破壞, 肺泡融合。海水組BALF 中蛋白滲出增加, 肺泡通透指數(shù)( PPI) 顯著增加。外周血WBC、血漿滲透壓、Na+ 、Cl - 、IL-1β、IL-8 和vWF 水平均進(jìn)行性升高。海水組傷后8 h 血漿 VEGF 及sVEGFR-1 表達(dá)明顯增加, 肺組織和BALF 中的VEGF 及sVEGFR-1 表達(dá)明顯減少。海水組血漿VEGF 水平增加與炎性因子、滲透壓增加呈正相關(guān)。結(jié)論 胸部開放傷海水浸泡致ALI 早期 VEGF 表達(dá)在血漿中明顯升高, 在肺組織和BALF 中明顯降低, 血漿VEGF 水平變化與海水高滲有明顯相關(guān)性。
引用本文: 胡曉紅,李毅,薛志強(qiáng),韓志海,段蘊(yùn)鈾. 胸部開放傷海水浸泡致急性肺損傷早期血管內(nèi)皮生長(zhǎng)因子水平變化. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2009, 09(5): 482-486. doi: 復(fù)制
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6. | Tsokos M, Pufe T, Paulsen F, et al. Pulmonary expression of vascular endothelial growth factor in sepsis. Arch Pathol Lab Med, 2003, 127: 331-335. |
7. | 姜曉暉, 王雪芬, 周永列, 等. 急性肺損傷早期支氣管肺泡灌洗液中VEGF 變化的研究. 浙江醫(yī)學(xué), 2005, 27: 659-661. |
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10. | Kaner RJ, Crystal RG. Compartmentalization of vascular endothelial growth factor to the epithelial surface of the human lung. Mol Med, 2001, 7: 240-246. |
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12. | Thickett DR, Armstrong L, Christie SJ, et al. Vascular endothelial growth factor may contribute to increased vascular permeability in acute respiratory distress syndrome. Am J Respir Crit Care Med, 2001, 164: 1601-1605. |
13. | Maitre B, Boussat S, Jean D, et al. Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury. Eur Respir J, 2001, 18: 100-106. |
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- 1. 沈宏亮, 王強(qiáng). 海水浸泡創(chuàng)傷病理生理變化和救治措施的研究進(jìn)展. 第二軍醫(yī)大學(xué)學(xué)報(bào), 2003, 24: 1365-1367.
- 2. 虞積耀, 賴西南, 李輝, 等. 戰(zhàn)傷合并海水浸泡生存時(shí)間及死亡率的動(dòng)物實(shí)驗(yàn)研究. 解放軍醫(yī)學(xué)雜志, 2005, 30: 268-269.
- 3. Ferrara N. Vascular endothelial growth factor and the regulation of angiogenesis. Recent Prog Horm Res, 2000, 55: 15-35.
- 4. Thickett DR, Armstrong L, and Millar AB. A role for vascular endothelial growth factor in acute and resolving lung injury. Am J Respir Crit Care Med, 2002 , 166: 1332 -1337 .
- 5. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med, 2003, 9: 669-676.
- 6. Tsokos M, Pufe T, Paulsen F, et al. Pulmonary expression of vascular endothelial growth factor in sepsis. Arch Pathol Lab Med, 2003, 127: 331-335.
- 7. 姜曉暉, 王雪芬, 周永列, 等. 急性肺損傷早期支氣管肺泡灌洗液中VEGF 變化的研究. 浙江醫(yī)學(xué), 2005, 27: 659-661.
- 8. 孟激光, 段蘊(yùn)鈾, 薛志強(qiáng), 等. 胸部開放傷后海水灌入胸腔致急性肺損傷犬模型的實(shí)驗(yàn)研究. 中華航海醫(yī)學(xué)與高氣壓醫(yī)學(xué)雜志, 2008, 15: 74-77.
- 9. Koyama S, Sato E, Haniuda M, et al. Decreased level of vascular endothelial growth factor in bronchoalveolar lavage fluid of normal smokers and patients with pulmonary fibrosis. Am J Respir Crit Care Med, 2002, 166: 382-385.
- 10. Kaner RJ, Crystal RG. Compartmentalization of vascular endothelial growth factor to the epithelial surface of the human lung. Mol Med, 2001, 7: 240-246.
- 11. Partovian C, Adnot S, Eddahibi S, et al. Heart and lung VEGF mRNA expression in rate with monocrotaline or hypoxia-induced pulmonary hypertension. Am J Physiol, 1998, 275: H1948-H1956.
- 12. Thickett DR, Armstrong L, Christie SJ, et al. Vascular endothelial growth factor may contribute to increased vascular permeability in acute respiratory distress syndrome. Am J Respir Crit Care Med, 2001, 164: 1601-1605.
- 13. Maitre B, Boussat S, Jean D, et al. Vascular endothelial growth factor synthesis in the acute phase of experimental and clinical lung injury. Eur Respir J, 2001, 18: 100-106.
- 14. Kaner RJ, Ladetto JV, Singh R, et al. Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema. Am J Respir Cell Mol Biol, 2000, 22: 657-664.
- 15. Mura M, dos Santos CC, Stewart D, et al. Vascular endothelial growth factor and related molecules in acute lung injury. J Appl Physiol, 2004, 97: 1605-1617.
- 16. Fehrenbach A, Pufe T, Wittwer T, et al. Reduced vascular endothelial growth factor correlates with alveolar epithelial damage after experimental ischemia and reperfusion. J Heart Lung Transplant, 2003, 22: 967-978.
- 17. Koehne P, Willam C, Strauss E, et, al. Lack of hypoxic stimulation of VEGF secretion from neutrophils and platelets. Am J Physiol Heart Circ Physiol, 2000, 279: H817-H824.
- 18. Haddad el-B, McCluskie K, Birrell MA, et al. Differential effects of ebselen on neutrophil recruitment, chemokine, and inflammatory mediator expression in a rat model of lipopolysaccharide-induced pulmonary inflammation. J Immunol, 2002, 169: 974-982.
- 19. Mukaida N. Pathophysiological roles of interleukin-8 / CXCL8 in pulmonary diseases. Am J Physiol Lung Cell Mol Physiol, 2003 , 284: L566-L577.
- 20. Shames BD, Zallen GS, McIntyre RC Jr, et al. Chemokines as mediators of diseases related to surgical conditions. Shock, 2000,14: 1.
- 21. Riffo-Vasquez Y, Spina D. Role of cytokines and chemokines in bronchial hyperresponsiveness and airway inflammation. Pharmacol Ther, 2002, 94: 185-211.
- 22. Varol E, Ozaydin M, Sahin M, et al. vWf levels as a circulating marker of endothelial dysfunction in patients with hypertrophic cardiomyopathy. Indian Heart J, 2005, 57: 655-657.