FLIP 腺病毒提升大鼠肺組織FLIP 表達及其對急性肺損傷防治作用的研究_《中國呼吸與危重監護雜志》

作者：

王文雅 ¹ , 屈朔瑤 ¹ , 歐陽海峰 ¹ , 黃蕓 ^1,2 , 吳朔 ¹ , 吳昌歸 ¹

1 第四軍醫大學西京醫院呼吸內科( 陜西西安 710032) ;;
2 解放軍第533 醫院( 云南昆明 650225)通訊作者: 吳昌歸, Email: changgui@ fmmu. edu. cn;

關鍵詞：

急性肺損傷 Fas 相關死亡域樣白介素1β轉換酶抑制蛋白腺病毒

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目的觀察Fas 相關死亡域樣白介素1β轉換酶抑制蛋白( FLIP) 重組體腺病毒滴鼻吸入對大鼠肺組織FLIP表達的影響以及對急性肺損傷( ALI) 的防治效果。方法 48 只SD 大鼠隨機分為4 組, 每組12 只。FLIP治療組: 脂多糖( LPS) 腹腔注射法建立大鼠ALI 模型, 制模后給予Ad-FLIP腺病毒滴鼻吸入; FLIP 預防組: 先以Ad-FLIP 腺病毒感染大鼠然后復制ALI 模型。對照治療組和對照預防組則分別在制模之后和之前, 給予增強型綠色熒光蛋白( EGFP) 腺病毒載體作為對照。觀察各組大鼠的一般情況和肺大體標本, 光鏡下觀察肺組織病理學改變, 測定肺組織濕干重比( W/D) 和肺通透性指數( LPI) 。采用RT-PCR、免疫組化法檢測并比較各組肺組織FLIP 的表達水平。結果 FLIP治療組和預防組與各對照組相比, 大鼠一般情況較好, 肺大體標本和組織病理學改變減輕, 肺組織濕干重比、肺通透性指數降低, 肺組織FLIP 的mRNA 和蛋白表達水平均顯著增高( P lt; 0. 01) 。結論滴鼻吸入FLIP 重組體腺病毒能夠上調大鼠肺組織的FLIP 表達, 保護肺呼吸膜, 減輕肺水腫,對大鼠ALI 有一定防治作用。

引用本文： 王文雅,屈朔瑤,歐陽海峰,黃蕓,吳朔,吳昌歸. FLIP 腺病毒提升大鼠肺組織FLIP 表達及其對急性肺損傷防治作用的研究. 中國呼吸與危重監護雜志, 2010, 9(2): 158-162. doi: 復制

1.	Esper AM, Martin GS. Evolution of treatments for patients with acute lung injury. Expert Opin Investig Drugs, 2005 , 14: 633 -645.
2.	de Souza PM, Lindsay MA. Apoptosis as a therapeutic target for the treatment of lung disease. Curr Opin Pharmacol, 2005 , 5: 232-237 .
3.	Li X, Shu R, Filippatos G, et al. Apoptosis in lung injury and remodeling. J Appl Physiol. 2004, 97: 1535-1542.
4.	Nastiuk KL, Yoo K, Lo K, et al. FLICE-like inhibitory protein blocks transforming growth factor beta 1-induced caspase activation and apoptosis in prostate epithelial cells. Mol Cancer Res, 2008, 6 :231 -242.
5.	屈朔瑤, 歐陽海峰, 遆新宇, 等. FLIP 腺病毒表達載體的構建及其在大鼠肺血管內皮細胞中的表達. 第四軍醫大學報, 2009 ,30: 1746-1748.
6.	薛昀, 吳新民, 張生鎖, 等. 內毒素預處理對大鼠急性肺損傷的影響. 中國危重病急救醫學, 2004, 16 : 361-363.
7.	Derks CM, Jacoboritz-Derks D. Embolic pneumopathy induced by oleic acid. A systematic morphologic. Am J Pathol, 1977 , 87: 143 -158 .
8.	Ware LB, Kaner RJ, Crystal RG, et al. VEGF levels in the alveolar compartment do not distinguish between ARDS and hydrostatic pulmonary oedema. Eur Respir J, 2005 , 26 : 101-105.
9.	Newton CJ, Xie YX, Burgoyne CH, et al. Fluvastatin induces apoptosis of vascular endothelial cells: blockade by glucocorticoids.Cardiovasc Surg, 2003, 11: 52-60 .
10.	Maniatis NA, Kotanidou A, Catravas JD, et al. Endothelial pathomechanisms in acute lung injury. Vascul Pharmacol, 2008, 49 :119-133.
11.	Gropper MA, Wiener-Kronish J. The epithelium in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care,2008, 14: 11 -15 .
12.	Kuwano K. Epithelial cell apoptosis and lung remodeling. Cell Mol Immunol, 2007, 4 : 419-429 .
13.	Macredmond R, Singhera GK, Dorscheid DR. Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute lung injurg. Eur Respir J, 2009, 33: 1403-1414.
14.	Srinivasula SM, Ahmad M, Ottilie S, et al. FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/ TNFR1 -induced apoptosis. J Biol Chem, 1997, 272: 18542-18545.
15.	Boatright KM, Deis C, Denault JB, et al. Activation of caspases-8 and-10 by FLIP ( L) . BiochemJ, 2004, 382: 651 -657.
16.	Erwert RD, Winn RK, Harlan JM, et al. Shiga-like toxin inhibition of FLICE-like inhibitory protein expression sensitizes endothelial cells to bacterial lipopolysaccharide-induced apoptosis. J BiolChem, 2002, 277: 40567 -40574.
17.	Cudrici C, Niculescu F, Jensen T, et al. C5b-9 terminal complex protects oligodendrocytes from apoptotic cell death by inhibiting caspase-8 processing and up-regulating FLIP. J Immunol, 2006 ,176: 3173-3180.

1. Esper AM, Martin GS. Evolution of treatments for patients with acute lung injury. Expert Opin Investig Drugs, 2005 , 14: 633 -645.
2. de Souza PM, Lindsay MA. Apoptosis as a therapeutic target for the treatment of lung disease. Curr Opin Pharmacol, 2005 , 5: 232-237 .
3. Li X, Shu R, Filippatos G, et al. Apoptosis in lung injury and remodeling. J Appl Physiol. 2004, 97: 1535-1542.
4. Nastiuk KL, Yoo K, Lo K, et al. FLICE-like inhibitory protein blocks transforming growth factor beta 1-induced caspase activation and apoptosis in prostate epithelial cells. Mol Cancer Res, 2008, 6 :231 -242.
5. 屈朔瑤, 歐陽海峰, 遆新宇, 等. FLIP 腺病毒表達載體的構建及其在大鼠肺血管內皮細胞中的表達. 第四軍醫大學報, 2009 ,30: 1746-1748.
6. 薛昀, 吳新民, 張生鎖, 等. 內毒素預處理對大鼠急性肺損傷的影響. 中國危重病急救醫學, 2004, 16 : 361-363.
7. Derks CM, Jacoboritz-Derks D. Embolic pneumopathy induced by oleic acid. A systematic morphologic. Am J Pathol, 1977 , 87: 143 -158 .
8. Ware LB, Kaner RJ, Crystal RG, et al. VEGF levels in the alveolar compartment do not distinguish between ARDS and hydrostatic pulmonary oedema. Eur Respir J, 2005 , 26 : 101-105.
9. Newton CJ, Xie YX, Burgoyne CH, et al. Fluvastatin induces apoptosis of vascular endothelial cells: blockade by glucocorticoids.Cardiovasc Surg, 2003, 11: 52-60 .
10. Maniatis NA, Kotanidou A, Catravas JD, et al. Endothelial pathomechanisms in acute lung injury. Vascul Pharmacol, 2008, 49 :119-133.
11. Gropper MA, Wiener-Kronish J. The epithelium in acute lung injury/acute respiratory distress syndrome. Curr Opin Crit Care,2008, 14: 11 -15 .
12. Kuwano K. Epithelial cell apoptosis and lung remodeling. Cell Mol Immunol, 2007, 4 : 419-429 .
13. Macredmond R, Singhera GK, Dorscheid DR. Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute lung injurg. Eur Respir J, 2009, 33: 1403-1414.
14. Srinivasula SM, Ahmad M, Ottilie S, et al. FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/ TNFR1 -induced apoptosis. J Biol Chem, 1997, 272: 18542-18545.
15. Boatright KM, Deis C, Denault JB, et al. Activation of caspases-8 and-10 by FLIP ( L) . BiochemJ, 2004, 382: 651 -657.
16. Erwert RD, Winn RK, Harlan JM, et al. Shiga-like toxin inhibition of FLICE-like inhibitory protein expression sensitizes endothelial cells to bacterial lipopolysaccharide-induced apoptosis. J BiolChem, 2002, 277: 40567 -40574.
17. Cudrici C, Niculescu F, Jensen T, et al. C5b-9 terminal complex protects oligodendrocytes from apoptotic cell death by inhibiting caspase-8 processing and up-regulating FLIP. J Immunol, 2006 ,176: 3173-3180.

《中國呼吸與危重監護雜志》

FLIP 腺病毒提升大鼠肺組織FLIP 表達及其對急性肺損傷防治作用的研究

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《中國呼吸與危重監護雜志》

FLIP 腺病毒提升大鼠肺組織FLIP 表達及其對急性肺損傷防治作用的研究

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