目的 明確哮喘大鼠肺T淋巴細(xì)胞中的組蛋白去乙?；?( HDAC1) 蛋白表達(dá)水平及組蛋白整體乙酰化和甲基化水平, 探討其在哮喘發(fā)病機(jī)制中的作用。方法 16 只Wistar 大鼠隨機(jī)分為對(duì)照組和哮喘組( 每組8 只) , 用卵白蛋白( OVA) 致敏并激發(fā)建立哮喘大鼠模型。通過哮喘臨床表現(xiàn)、氣道高反應(yīng)性測(cè)定、肺組織HE 染色、血清和BALF中細(xì)胞因子IL-4、γ干擾素( IFN-γ) 及IgEELISA 測(cè)定, 判斷哮喘大鼠模型是否成功。分離肺T 細(xì)胞并進(jìn)行純度鑒定。Western blot 檢測(cè)肺T細(xì)胞HDAC1 蛋白表達(dá)水平, 組蛋白H3、H4 整體乙酰化, 以及H3k9 整體二甲基化水平。結(jié)果 與對(duì)照組比較, 哮喘組HDAC1 蛋白表達(dá)水平低于對(duì)照組( P lt; 0. 05) , 組蛋白H3、H4 整體乙?；胶虷3k9 整體二甲基化水平差異均無統(tǒng)計(jì)學(xué)意義。結(jié)論 肺T 細(xì)胞HDAC1 可能參與了支氣管哮喘的發(fā)病環(huán)節(jié), 組蛋白整體乙?；图谆脚c哮喘發(fā)病無明顯相關(guān)性, HDAC1 對(duì)組蛋白修飾作用可能是一個(gè)基因轉(zhuǎn)錄特異性事件。
引用本文： 李成業(yè),郭雪君,甘麗杏,丁濤,顧問. 哮喘大鼠肺T 細(xì)胞中組蛋白去乙?；? 的表達(dá)及對(duì)組蛋白修飾的影響. 中國(guó)呼吸與危重監(jiān)護(hù)雜志, 2010, 9(3): 259-263. doi: 復(fù)制
| 1. | Kaminuma O, Kitamura F, Miyatake S, et al. T-box 21 transcription factor is responsible for distorted T( H) 2 differentiation in human peripheral CD4 + T cells. J Allergy Clin Immunol,2009, 123: 813-23. |
| 2. | Su RC, Becker AB, Kozyrskyj AL, et al. Epigenetic regulation of established human type 1 versus type 2 cytokine responses. JAllergyClin Immunol, 2008, 121: 57-63. |
| 3. | 李成業(yè), 甘麗杏, 郭雪君. 支氣管哮喘的表觀遺傳學(xué). 中華結(jié)核和呼吸雜志, 2009, 32 : 759-761. |
| 4. | Ito K, Caramori G, Lim S, et al. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med, 2002, 166 : 392-396. |
| 5. | Miller RL, Ho SM. Environmental Epigenetics and Asthma. Am J Respir Crit Care Med, 2008 , 177: 567-573 . |
| 6. | El-Biaze M, Boniface S, Koscher V, et al. T cell activation, from atopy to asthma: more a paradox. Allergy, 2003 , 58: 844-853. |
| 7. | Marmorstein R. Protein modules that manipulate histone tails for chromatin regulation. Nat Rev Mol Cell Biol, 2001, 2: 422-432. |
| 8. | Bhavsar P, Ahmad T, Adcock IM. The role of histone deacetylases in asthma and allergic diseases. J Allergy Clin Immunol, 2008, 121 :580-584. |
| 9. | Workman JL, Kingston RE. Alteration of nucleosome structure as a mechanismof transcriptional regulation. Annu Rev Biochem, 1998 ,67: 545-579 . |
| 10. | Peterson S, Jackson V. Acetylation of H4 suppresses the repressive effects of the N-termini of histones H3 /H4 and facilitates the formation of positively coiled DNA. Biochemistry, 2008 , 47: 7053 -7065. |
| 11. | Ito K, Charron CE, Adcock IM. Impact of protein acetylation in inflammatory lung diseases. Pharmacol Ther, 2007, 116 : 249-265. |
| 12. | Bannister AJ, Kouzarides T. Reversing histone methylation. Nature,2005, 436: 1103-1106. |
| 13. | Weichert W. HDAC expression and clinical prognosis in human malignancies. Cancer Lett, 2009, 280 : 168-176. |
| 14. | Heinzel T, Lavinsky RM, Mullen TM, et al. A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature, 1997 , 387: 43-48 . |
| 15. | Moreira JM, Scheipers P, S??rensen P. The histone deacetylase inhibitor Trichostatin A modulates CD4 + T cell responses. BMC Cancer, 2003 , 3: 30 . |
| 16. | Choi JH, Oh SW, Kang MS, et al. Trichostatin A attenuates airway inflammation in mouse asthma model. Clin Exp Allergy, 2005, 35 :89-96. |
| 17. | Ma P, Schultz RM. Histone deacetylase 1 ( HDAC1 ) regulates histone acetylation, development, and gene expression in preimplantation mouse embryos. Dev Biol, 2008, 319 : 110-120. |
- 1. Kaminuma O, Kitamura F, Miyatake S, et al. T-box 21 transcription factor is responsible for distorted T( H) 2 differentiation in human peripheral CD4 + T cells. J Allergy Clin Immunol,2009, 123: 813-23.
- 2. Su RC, Becker AB, Kozyrskyj AL, et al. Epigenetic regulation of established human type 1 versus type 2 cytokine responses. JAllergyClin Immunol, 2008, 121: 57-63.
- 3. 李成業(yè), 甘麗杏, 郭雪君. 支氣管哮喘的表觀遺傳學(xué). 中華結(jié)核和呼吸雜志, 2009, 32 : 759-761.
- 4. Ito K, Caramori G, Lim S, et al. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med, 2002, 166 : 392-396.
- 5. Miller RL, Ho SM. Environmental Epigenetics and Asthma. Am J Respir Crit Care Med, 2008 , 177: 567-573 .
- 6. El-Biaze M, Boniface S, Koscher V, et al. T cell activation, from atopy to asthma: more a paradox. Allergy, 2003 , 58: 844-853.
- 7. Marmorstein R. Protein modules that manipulate histone tails for chromatin regulation. Nat Rev Mol Cell Biol, 2001, 2: 422-432.
- 8. Bhavsar P, Ahmad T, Adcock IM. The role of histone deacetylases in asthma and allergic diseases. J Allergy Clin Immunol, 2008, 121 :580-584.
- 9. Workman JL, Kingston RE. Alteration of nucleosome structure as a mechanismof transcriptional regulation. Annu Rev Biochem, 1998 ,67: 545-579 .
- 10. Peterson S, Jackson V. Acetylation of H4 suppresses the repressive effects of the N-termini of histones H3 /H4 and facilitates the formation of positively coiled DNA. Biochemistry, 2008 , 47: 7053 -7065.
- 11. Ito K, Charron CE, Adcock IM. Impact of protein acetylation in inflammatory lung diseases. Pharmacol Ther, 2007, 116 : 249-265.
- 12. Bannister AJ, Kouzarides T. Reversing histone methylation. Nature,2005, 436: 1103-1106.
- 13. Weichert W. HDAC expression and clinical prognosis in human malignancies. Cancer Lett, 2009, 280 : 168-176.
- 14. Heinzel T, Lavinsky RM, Mullen TM, et al. A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature, 1997 , 387: 43-48 .
- 15. Moreira JM, Scheipers P, S??rensen P. The histone deacetylase inhibitor Trichostatin A modulates CD4 + T cell responses. BMC Cancer, 2003 , 3: 30 .
- 16. Choi JH, Oh SW, Kang MS, et al. Trichostatin A attenuates airway inflammation in mouse asthma model. Clin Exp Allergy, 2005, 35 :89-96.
- 17. Ma P, Schultz RM. Histone deacetylase 1 ( HDAC1 ) regulates histone acetylation, development, and gene expression in preimplantation mouse embryos. Dev Biol, 2008, 319 : 110-120.