胸部開放傷海水浸泡致急性肺損傷早期血管內皮生長因子水平變化_《中國呼吸與危重監護雜志》

作者：

胡曉紅 ^1,2 , 李毅 ³ , 薛志強 ⁴ , 韓志海 ³ ,  段蘊鈾 ³

1 軍事醫學科學院研究生隊(北京 100850);;
2 海軍總醫院兒科(北京 100048);;
3 海軍總醫院呼吸科(北京 100048)4 解放軍總醫院胸外科(北京 100853);

關鍵詞：

急性肺損傷海水胸部開放傷血管內皮生長因子血管內皮生長因子受體

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目的觀察胸部開放傷海水浸泡致ALI 早期血管內皮生長因子( 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 表達在胸部開放傷海水浸泡致ALI 發病機制中的作用。方法 16 只成年雜交犬隨機分為對照組( 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, 監測生命體征并取動、靜脈血。測定各時相點外周血白細胞計數( WBC) 、血氣、電解質和血漿滲透壓, 采用ELISA 法檢測血漿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BALF 及肺組織勻漿中VEGF 及受體sVEGFR-1 水平。測定傷后8 h BALF 和血漿中蛋白含量, 并計算肺泡通透指數( BALF中蛋白含量/ 血漿蛋白含量) 。結果與對照組比較, 海水組肺組織病理切片見毛細血管擴張淤血嚴重, 肺間質和肺泡腔內有大量水腫液積聚, 部分肺泡結構的完整性破壞, 肺泡融合。海水組BALF 中蛋白滲出增加, 肺泡通透指數( PPI) 顯著增加。外周血WBC、血漿滲透壓、Na+ 、Cl - 、IL-1β、IL-8 和vWF 水平均進行性升高。海水組傷后8 h 血漿 VEGF 及sVEGFR-1 表達明顯增加, 肺組織和BALF 中的VEGF 及sVEGFR-1 表達明顯減少。海水組血漿VEGF 水平增加與炎性因子、滲透壓增加呈正相關。結論胸部開放傷海水浸泡致ALI 早期 VEGF 表達在血漿中明顯升高, 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性。

引用本文： 胡曉紅,李毅,薛志強,韓志海,段蘊鈾. 胸部開放傷海水浸泡致急性肺損傷早期血管內皮生長因子水平變化. 中國呼吸與危重監護雜志, 2009, 09(5): 482-486. doi: 復制

1.	沈宏亮, 王強. 海水浸泡創傷病理生理變化和救治措施的研究進展. 第二軍醫大學學報, 2003, 24: 1365-1367.
2.	虞積耀, 賴西南, 李輝, 等. 戰傷合并海水浸泡生存時間及死亡率的動物實驗研究. 解放軍醫學雜志, 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. 浙江醫學, 2005, 27: 659-661.
8.	孟激光, 段蘊鈾, 薛志強, 等. 胸部開放傷后海水灌入胸腔致急性肺損傷犬模型的實驗研究. 中華航海醫學與高氣壓醫學雜志, 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.

1. 沈宏亮, 王強. 海水浸泡創傷病理生理變化和救治措施的研究進展. 第二軍醫大學學報, 2003, 24: 1365-1367.
2. 虞積耀, 賴西南, 李輝, 等. 戰傷合并海水浸泡生存時間及死亡率的動物實驗研究. 解放軍醫學雜志, 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. 浙江醫學, 2005, 27: 659-661.
8. 孟激光, 段蘊鈾, 薛志強, 等. 胸部開放傷后海水灌入胸腔致急性肺損傷犬模型的實驗研究. 中華航海醫學與高氣壓醫學雜志, 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.

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