Regulation of CⅡTA to Major Histocompatibility Complex Class Ⅱ Gene in Multiple Organ Dysfunction Syndrome_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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柴琛 , 薛左良 , 曹农 , 王斌生 , 李强

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Keywords：

反式转录因子; 多器官功能障碍综合征; 动物模型; MHCⅡ类基因

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目的探讨主要组织相容性复合体(MHC)Ⅱ类基因的反式转录因子（CⅡTA）在多器官功能障碍综合征（MODS）中对MHCⅡ类基因的调控机理。方法 18只雄性家猪随机分为实验组（n=9）和对照组(n=9)。实验组给予失血性休克、再灌注损伤、内毒素血症等复合干扰因素，建立二次打击猪MODS模型；对照组仅进行麻醉和动静脉插管。7 d后处死存活动物。切取实验组造模成功动物和对照组动物的脾脏组织，用Trizol法提取总RNA。设计CⅡTA和猪MHCⅡ类基因(SLA-DQA)引物序列，逆转录构建cDNA，行实时荧光定量PCR检测。UVP计算机图像分析系统绘出标准曲线并得出2组CⅡTA mRNA和SLA-DQA mRNA的拷贝数。以Pearson法分析MODS动物CⅡTA mRNA和SLA-DQA mRNA表达的相关性。结果实验组动物死亡7例，有8例发生MODS。对照组动物CⅡTA mRNA的拷贝数为（3.516±1.237）×103，实验组MODS动物为（0.367±0.088）×103，差异有统计学意义（P=0.000）；对照组SLA-DQA mRNA拷贝数为（5.330±3.053）×103，实验组为（1.376±1.006）×103，差异亦有统计学意义(P=0.002)。MODS动物中CⅡTA mRNA和SLA-DQA mRNA的表达呈正相关(Pearson值为0.499，P=0.017)。结论 MODS模型复制满意。MHCⅡ类基因在MODS中表达下降与CⅡTA的调控有关。

Citation： 柴琛,薛左良,曹农,王斌生,李强. Regulation of CⅡTA to Major Histocompatibility Complex Class Ⅱ Gene in Multiple Organ Dysfunction Syndrome. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(11): 1190-1192. doi: Copy

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5.	Steimle V, Otten LA, Zufferey M, et al. Complementation cloning of an MHC class Ⅱ transactivator mutated in hereditary MHC class Ⅱ deficiency (or bare lymphocyte syndrome) [J]. Cell, 1993; 75(1): 135-146.
6.	Harton JA, Ting JP. Class Ⅱ transactivator: mastering the art of major histocompatibility complex expression [J]. Mol Cell Biol, 2000; 20(17): 6185-6194.
7.	Steimle V, Siegrist CA, Mottet A, et al. Regulation of MHC class Ⅱ expression by interferon-gamma mediated by the transactivator gene CⅡTA [J]. Science, 1994; 265(5168): 106-109.
8.	Otten LA, Steimle V, Bontron S, et al. Quantitative control of MHC class Ⅱ expression by the transactivator CⅡTA [J]. Eur J Immunol, 1998; 28(2): 473-478.
9.	Peretti M, Villard J, Barras E, et al. Expression of the three human major histocompatibility complex class Ⅱ isotypes exhibits a differential dependence on the transcription factor RFXAP [J]. Mol Cell Biol, 2001; 21(17): 5699-5709.
10.	Kanazawa S, Okamoto T, Peterlin BM. Tat competes with CⅡTA for the binding to P-TEFb and blocks the expression of MHC class Ⅱ genes in HIV infection [J]. Immunity, 2000; 12(1): 61-70.
11.	Schooten E, Klous P, van den Elsen PJ, et al. Lack of MHC-Ⅱ expression in activated mouse T cells correlates with DNA methylation at the CⅡTA-PⅢ region [J]. Immunogenetics, 2005; 57(10): 795-799.
12.	欧启水, 林琪, 兰斌，等. CⅡTA基因修饰树突状细胞增强荷肝癌小鼠抗瘤效应 [J]. 细胞与分子免疫学杂志， 2005; 21(5): 580-582, 586.

1. 柴琛，方国恩，沈贤，等. 主要组织相容性复合体Ⅱ类基因在多器官功能障碍综合征中的表达及意义 [J]. 中华创伤杂志， 2006; 22(11): 839-842.
2. Hu S, Sheng Z, Zhou B, et al. Study on delay two-phase multiple organ dysfunction syndrome [J]. Chin Med J (Engl), 1998; 111(2): 101-108.
3. Friese MA, Jones EY, Fugger L. MHC Ⅱ molecules in inflammatory diseases: interplay of qualities and quantities [J]. Trends Immunol, 2005; 26(11): 559-561.
4. Pachot A, Monneret G, Brion A, et al. Messenger RNA expression of major histocompatibility complex class Ⅱ genes in whole blood from septic shock patients [J]. Crit Care Med, 2005; 33(1): 31-38.
5. Steimle V, Otten LA, Zufferey M, et al. Complementation cloning of an MHC class Ⅱ transactivator mutated in hereditary MHC class Ⅱ deficiency (or bare lymphocyte syndrome) [J]. Cell, 1993; 75(1): 135-146.
6. Harton JA, Ting JP. Class Ⅱ transactivator: mastering the art of major histocompatibility complex expression [J]. Mol Cell Biol, 2000; 20(17): 6185-6194.
7. Steimle V, Siegrist CA, Mottet A, et al. Regulation of MHC class Ⅱ expression by interferon-gamma mediated by the transactivator gene CⅡTA [J]. Science, 1994; 265(5168): 106-109.
8. Otten LA, Steimle V, Bontron S, et al. Quantitative control of MHC class Ⅱ expression by the transactivator CⅡTA [J]. Eur J Immunol, 1998; 28(2): 473-478.
9. Peretti M, Villard J, Barras E, et al. Expression of the three human major histocompatibility complex class Ⅱ isotypes exhibits a differential dependence on the transcription factor RFXAP [J]. Mol Cell Biol, 2001; 21(17): 5699-5709.
10. Kanazawa S, Okamoto T, Peterlin BM. Tat competes with CⅡTA for the binding to P-TEFb and blocks the expression of MHC class Ⅱ genes in HIV infection [J]. Immunity, 2000; 12(1): 61-70.
11. Schooten E, Klous P, van den Elsen PJ, et al. Lack of MHC-Ⅱ expression in activated mouse T cells correlates with DNA methylation at the CⅡTA-PⅢ region [J]. Immunogenetics, 2005; 57(10): 795-799.
12. 欧启水, 林琪, 兰斌，等. CⅡTA基因修饰树突状细胞增强荷肝癌小鼠抗瘤效应 [J]. 细胞与分子免疫学杂志， 2005; 21(5): 580-582, 586.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Regulation of CⅡTA to Major Histocompatibility Complex Class Ⅱ Gene in Multiple Organ Dysfunction Syndrome

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