目的 觀察姜黃素誘導(dǎo)特發(fā)性肺纖維化( IPF) 患者肺成纖維細(xì)胞凋亡的作用, 探討相關(guān)分子機(jī)制。方法 體外培養(yǎng)開(kāi)胸肺活檢IPF 患者的肺成纖維細(xì)胞。采用不同濃度姜黃素( 5、10、20及40 μmol /L) 作用于肺成纖維細(xì)胞。MTT 法檢測(cè)姜黃素對(duì)肺成纖維細(xì)胞增殖的抑制作用, 計(jì)算細(xì)胞抑制率; 應(yīng)用流式細(xì)胞術(shù)檢測(cè)細(xì)胞凋亡以及凋亡相關(guān)基因半胱氨酸天冬氨酸蛋白酶3( Caspase-3) 的表達(dá)。采用SPSS11. 5 軟件進(jìn)行統(tǒng)計(jì)學(xué)分析, 多組數(shù)據(jù)間比較采用單因素方差分析, 采用Pearson 相關(guān)分析進(jìn)行相關(guān)性檢驗(yàn)。結(jié)果 5 ～40 μmol / L 姜黃素作用于肺成纖維細(xì)胞不同時(shí)間( 6、12、24 及48 h)后, 對(duì)細(xì)胞增殖具有明顯抑制作用, 呈劑量-時(shí)間效應(yīng)關(guān)系, 抑制率與濃度和時(shí)間均呈正相關(guān)( r =0. 886, r =0. 832, P 均 lt; 0. 01) 。流式細(xì)胞術(shù)檢測(cè)到細(xì)胞凋亡, 5 ～40 μmol /L 姜黃素作用后凋亡率分別為( 29. 58 ±2. 13) % 、( 64. 36 ±3. 92) %、( 72. 98 ±4. 42) % 和( 83. 14 ±2. 51) % , 與不加姜黃素的陰性對(duì)照組( 3. 84 ±1. 88) % 比較, 差異均有統(tǒng)計(jì)學(xué)意義( P lt;0. 01) ; Caspase-3 蛋白表達(dá)陽(yáng)性率分別為( 26. 24 ±3. 64) % 、( 44. 87 ±5. 31) % 、( 57. 44 ±4. 23) % 和( 73. 65 ±5. 01) % , 與不加姜黃素的陰性對(duì)照組( 4. 02 ±0. 62) %比較, 差異均有統(tǒng)計(jì)學(xué)意義( P lt;0. 01) 。結(jié)論 姜黃素可能通過(guò)激活Caspase-3,誘導(dǎo)IPF 患者肺成纖維細(xì)胞凋亡。
引用本文： 高蔚,張德平,陳碧. 姜黃素誘導(dǎo)人肺成纖維細(xì)胞凋亡的相關(guān)分子機(jī)制的初步研究. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2009, 09(2): 186-189. doi: 復(fù)制
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| 6. | Phan SH. The myofibroblast in pulmonary fibrosis. Chest, 2002 , 122( Suppl 6) : S286-S289. |
| 7. | Liu HL, Chen Y, Cui GH, et al. Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raj i proliferation. Acta Pharmacol Sin, 2005, 26 : 603-609. |
| 8. | 張德平, 邱慧, 莊誼. 姜黃素干預(yù)對(duì)博萊霉素誘導(dǎo)的大鼠肺纖維化的影響. 中華結(jié)核和呼吸雜志, 2007, 10: 197-201. |
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| 10. | Fan G, Ma X, Wong PY, et al. p53 dephosphorylation and p21 ( Cip1 /Waf1 ) translocation correlate with caspase-3 activation in TGF-beta1-induced apoptosis of HuH-7 cells. Apoptosis, 2004, 9:211-221. |
- 1. Punithavathi D, Venkatesan N, Babu M. Protective effects of curcumin against amiodarone-induced pulmonary fibrosis in rats. Br J Pharmacol, 2003, 139: 1342-1350.
- 2. 中華醫(yī)學(xué)會(huì)呼吸病學(xué)分會(huì). 特發(fā)性肺間質(zhì)纖維化診斷和治療指南( 草案) . 現(xiàn)代實(shí)用醫(yī)學(xué)雜志, 2003, 15: 129-131.
- 3. Willis BC, Liebler JM, Luby-Phelps K, et al. Induction of epithelialmesenchymal transition in alveolar epithelia1 cells by transforming growth factor-beta1: potential role in idiopathic pulmonary fibrosis.Am J Pathol, 2005, 166: 1321-1332.
- 4. Wang R, Ramos C, Joshi I, et al. Human lung myofibroblast-derived inducers of alveolar epithelial apoptosis identified as angiotensin peptides. Am J Physiol, 1999, 277: L1158-L1164.
- 5. Tourkina E, Gooz P, Oates JC, et al. Curcumin-induced apoptosis in scleroderma lung fibroblasts: role of protein kinase cepsilon. Am J Respir Cell Mol Biol, 2004, 31: 28-35.
- 6. Phan SH. The myofibroblast in pulmonary fibrosis. Chest, 2002 , 122( Suppl 6) : S286-S289.
- 7. Liu HL, Chen Y, Cui GH, et al. Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor regulating B-NHL cell line Raj i proliferation. Acta Pharmacol Sin, 2005, 26 : 603-609.
- 8. 張德平, 邱慧, 莊誼. 姜黃素干預(yù)對(duì)博萊霉素誘導(dǎo)的大鼠肺纖維化的影響. 中華結(jié)核和呼吸雜志, 2007, 10: 197-201.
- 9. 陳碧, 張德平. 姜黃素干預(yù)對(duì)實(shí)驗(yàn)性肺間質(zhì)纖維化的影響. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2007, 6: 208-212.
- 10. Fan G, Ma X, Wong PY, et al. p53 dephosphorylation and p21 ( Cip1 /Waf1 ) translocation correlate with caspase-3 activation in TGF-beta1-induced apoptosis of HuH-7 cells. Apoptosis, 2004, 9:211-221.