骨髓間質干細胞移植對博萊霉素誘導大鼠肺纖維化的治療作用_《中國呼吸與危重監護雜志》

作者：

王欣燕 ¹ ,  吳曉梅 ¹ , 康小文 ¹ , 黃昆 ¹ , 李波 ² , 陳復輝 ¹ , 白露 ¹

1 哈爾濱醫科大學附屬二院呼吸內科（黑龍江哈爾濱 150086）;;
2 哈爾濱市第一醫院呼吸科（黑龍江哈爾濱 150001）;

關鍵詞：

間充質干細胞干細胞移植腫瘤壞死因子α 轉化生長因子

視頻：

導出 下載 收藏 掃碼 引用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的研究骨髓間質干細胞( BMSCs) 對博萊霉素A5( BLMA5) 所致的大鼠肺間質纖維化的治療作用。方法收集、培養雄性SD 幼鼠( 鼠齡10 d) 的BMSCs, 并進行DAPI 標記。將70 只雌性SD 大鼠隨機分為4 組, A 組( n =21) : 生理鹽水對照組; B 組( n =21) : BLMA5 模型組; C組( n =21) : 氣管內注入BLMA5 后立即尾靜脈注射移植BMSCs; D 組( n=7) : 氣管內注入BLMA5 14 d 后移植BMSCs。分別于第7、14、28 d( D 組于第28 d) 處死大鼠, 取肺組織病理切片行HE 及Masson 染色觀察肺部炎癥和纖維化情況,熒光顯微鏡下檢測DAPI 標記細胞; PCR 法檢測睪丸決定因子( SRY) 基因; ELISA 法檢測肺組織內羥脯氨酸( HYP) 、TNF-α和TGF-β1 的含量。結果 ( 1) 在C、D 組7、14、28 d 肺組織冰凍切片中均見到DAPI 標記的BMSCs, PCR 檢測到雄性SD 大鼠SRY 基因。( 2) B 組第7 d 肺泡炎最明顯, 到28 d 時肺纖維化最嚴重,與其他三組比較差異均有統計學意義( P lt;0. 05 或0. 01) ; C、D 兩組肺泡炎及肺纖維化程度均較B 組顯著減輕( P lt;0. 05) , 但仍較A 組嚴重( P lt;0. 05 或0. 01) , 其中D 組較C 組嚴重( P lt;0. 05) 。( 3) B 組第7 dHYP 含量開始升高, 28 d 最高, 顯著高于其他三組( P lt;0. 05 或0. 01) , 各組變化趨勢與肺纖維化變化相一致; B組TNF-α在第7 d 最高, 此后開始下降, 在14 d 時仍高于A、C 兩組( P lt;0. 05) , 28 d 時四組之間無明顯差異; B組TGF-β1 在第28 d 達最高, 各組之間比較均有顯著差異( P lt;0. 05) 。結論骨髓間質干細胞可定植于損傷肺組織, 并能有效阻止BLMA5 誘導的大鼠肺纖維化, 且早期治療效果優于晚期。

引用本文： 王欣燕,吳曉梅,康小文,黃昆,李波,陳復輝,白露. 骨髓間質干細胞移植對博萊霉素誘導大鼠肺纖維化的治療作用. 中國呼吸與危重監護雜志, 2009, 09(1): 57-62. doi: 復制

1.	蔡后榮. 特發性肺纖維化: 治療還是等待? 中國呼吸與危重監護雜志, 2008, 7: 321-322.
2.	Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science, 1999, 284: 1168-1170.
3.	Miyazaki M, Akiyama I, Sakaguchi M, et al. Improved conditions to induce hepatocytes from rat bone marrow cells in culture. Bioch Bioph Res Comm, 2002, 298: 24-30.
4.	Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature, 2001, 410: 701-705.
5.	Kotton DN, Ma BY, Cardoso WV, et al. Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development, 2001, 128:5181-5188.
6.	Gaustad KG, Boquest AC, Anderson BE, et al. Differentiation of human adipose tissue stem cells using extracts of rat cardiomyocytes.Biochem Biophys Res Com, 2004, 314: 420-427.
7.	Rupp S, Badorff C, Koyanagi M, et al. Statin therapy in patients with coronary artery disease improves the impaired endothelial progenitor cell differentiation into cardiomyogenic cells. Basic Res Cardiol,2004, 99: 61-68.
8.	Woodbury D, Schwarz EJ, Prockop DJ, et al. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res,2000, 61: 364-370.
9.	Badiavas EV, Abedi M, Butmarc J, et al. Participation of bone marrow derived cells in cutaneous wound healing. J Cell Physiol,2003, 196: 245-250.
10.	Rojas M, Xu J, Woods CR, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol,2005, 33: 145-152.
11.	Chang JC, Summer R, Sun X. Evidence that bone marrow cells do not contribute to the alveolar epithelium. Am J Respir Cell Mol Biol,2005, 33: 335-342.
12.	王延華, 羊惠君, 主編. 干細胞理論與技術. 北京: 科學出版社,2005, 170-181.
13.	Tang DQ, Cao LZ, Burkhardt BR, et al. In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow.Diabetes, 2004, 53: 1721-1732.
14.	Szapiel SV, Elson NA, Fulmer JD, et al. Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis, 1979, 120 : 893-899.
15.	Gagliano N, Moscheni C, Dellavia C, et al. Immunosuppression and gingival overgrowth: gene and protein expression profiles of collagen turnover in FK506 -treated human gingival fibroblasts. J Clin Periodontol, 2005, 32: 167-173.
16.	Ortiz LA, Gambelli F, McBride C, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A, 2003 ,100: 8407-8411.
17.	Tran SD, Pillemer SR, Dutra A, et al. Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study. Lancet, 2003, 361: 1084-1088.
18.	Zhang K, Gharaee KM, McGarry B, et al. TNF-alpha-mediated lung cytokine networking and eosinophil recruitment in pulmonary fibrosis.J Immunol, 1997, 158: 954-959.
19.	Wang Q,Wang Y, Hyde DM, et al. Reduction of bleomycin induced lung fibrosis by transforming growth factor beta soluble receptor.Thorax, 1999, 54: 805-812.
20.	Nakao A, Fujii M, Matsumura R, et al. Transient gene transfer and expression of Smad7 prevents bleomycin-induced lung fibrosis in mice. J Clin Invest, 1999, 104: 5-11.
21.	Brass DM, Hoyle GW, Poovey HG. Reduced tumor necrosis factor-alpha and transforming growth factor-beta1 expression in the lungs of inbred mice that fail to develop fibroproliferative lesions consequent to asbestos exposure. Am J Pathol, 1999, 154: 853-862.

1. 蔡后榮. 特發性肺纖維化: 治療還是等待? 中國呼吸與危重監護雜志, 2008, 7: 321-322.
2. Petersen BE, Bowen WC, Patrene KD, et al. Bone marrow as a potential source of hepatic oval cells. Science, 1999, 284: 1168-1170.
3. Miyazaki M, Akiyama I, Sakaguchi M, et al. Improved conditions to induce hepatocytes from rat bone marrow cells in culture. Bioch Bioph Res Comm, 2002, 298: 24-30.
4. Orlic D, Kajstura J, Chimenti S, et al. Bone marrow cells regenerate infarcted myocardium. Nature, 2001, 410: 701-705.
5. Kotton DN, Ma BY, Cardoso WV, et al. Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development, 2001, 128:5181-5188.
6. Gaustad KG, Boquest AC, Anderson BE, et al. Differentiation of human adipose tissue stem cells using extracts of rat cardiomyocytes.Biochem Biophys Res Com, 2004, 314: 420-427.
7. Rupp S, Badorff C, Koyanagi M, et al. Statin therapy in patients with coronary artery disease improves the impaired endothelial progenitor cell differentiation into cardiomyogenic cells. Basic Res Cardiol,2004, 99: 61-68.
8. Woodbury D, Schwarz EJ, Prockop DJ, et al. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res,2000, 61: 364-370.
9. Badiavas EV, Abedi M, Butmarc J, et al. Participation of bone marrow derived cells in cutaneous wound healing. J Cell Physiol,2003, 196: 245-250.
10. Rojas M, Xu J, Woods CR, et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol,2005, 33: 145-152.
11. Chang JC, Summer R, Sun X. Evidence that bone marrow cells do not contribute to the alveolar epithelium. Am J Respir Cell Mol Biol,2005, 33: 335-342.
12. 王延華, 羊惠君, 主編. 干細胞理論與技術. 北京: 科學出版社,2005, 170-181.
13. Tang DQ, Cao LZ, Burkhardt BR, et al. In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow.Diabetes, 2004, 53: 1721-1732.
14. Szapiel SV, Elson NA, Fulmer JD, et al. Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis, 1979, 120 : 893-899.
15. Gagliano N, Moscheni C, Dellavia C, et al. Immunosuppression and gingival overgrowth: gene and protein expression profiles of collagen turnover in FK506 -treated human gingival fibroblasts. J Clin Periodontol, 2005, 32: 167-173.
16. Ortiz LA, Gambelli F, McBride C, et al. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A, 2003 ,100: 8407-8411.
17. Tran SD, Pillemer SR, Dutra A, et al. Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study. Lancet, 2003, 361: 1084-1088.
18. Zhang K, Gharaee KM, McGarry B, et al. TNF-alpha-mediated lung cytokine networking and eosinophil recruitment in pulmonary fibrosis.J Immunol, 1997, 158: 954-959.
19. Wang Q,Wang Y, Hyde DM, et al. Reduction of bleomycin induced lung fibrosis by transforming growth factor beta soluble receptor.Thorax, 1999, 54: 805-812.
20. Nakao A, Fujii M, Matsumura R, et al. Transient gene transfer and expression of Smad7 prevents bleomycin-induced lung fibrosis in mice. J Clin Invest, 1999, 104: 5-11.
21. Brass DM, Hoyle GW, Poovey HG. Reduced tumor necrosis factor-alpha and transforming growth factor-beta1 expression in the lungs of inbred mice that fail to develop fibroproliferative lesions consequent to asbestos exposure. Am J Pathol, 1999, 154: 853-862.

《中國呼吸與危重監護雜志》

骨髓間質干細胞移植對博萊霉素誘導大鼠肺纖維化的治療作用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

上一篇

下一篇

Format

Content

《中國呼吸與危重監護雜志》

骨髓間質干細胞移植對博萊霉素誘導大鼠肺纖維化的治療作用

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

上一篇

下一篇

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料