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中华危重症医学杂志(电子版) ›› 2017, Vol. 10 ›› Issue (03) : 149 -152. doi: 10.3877/cma.j.issn.1674-6880.2017.03.002

所属专题: 文献

论著

乌司他丁对脓毒症小鼠调节性T细胞凋亡及细胞因子分泌的影响
曹超1, 柴艳芬1,(), 寿松涛1, 王军1   
  1. 1. 300052 天津,天津医科大学总医院急诊医学科
  • 收稿日期:2016-06-16 出版日期:2017-06-01
  • 通信作者: 柴艳芬
  • 基金资助:
    天津市应用基础与前沿技术研究计划项目(13JCYBJC37500); 睿E(睿医)急诊医学研究专项基金项目(R2015026); 天普研究基金项目(UF201315); 天津医科大学总医院青年孵育基金项目(ZYYFY2015010)

Effect of ulinastatin on the apoptosis of regulatory T cells and cytokine secretion in septic mice

Chao Cao1, Yanfen Chai1,(), Songtao Shou1, Jun Wang1   

  1. 1. Department of Emergency, Tianjin Medical University General Hospital, Tianjin 300052, China
  • Received:2016-06-16 Published:2017-06-01
  • Corresponding author: Yanfen Chai
  • About author:
    Corresponding author: Chai Yanfen, Email: chaiyanfen2012@126.com.
引用本文:

曹超, 柴艳芬, 寿松涛, 王军. 乌司他丁对脓毒症小鼠调节性T细胞凋亡及细胞因子分泌的影响[J/OL]. 中华危重症医学杂志(电子版), 2017, 10(03): 149-152.

Chao Cao, Yanfen Chai, Songtao Shou, Jun Wang. Effect of ulinastatin on the apoptosis of regulatory T cells and cytokine secretion in septic mice[J/OL]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2017, 10(03): 149-152.

目的

观察乌司他丁对脓毒症小鼠调节性T细胞(Treg)凋亡及细胞因子分泌的影响。

方法

将60只小鼠分为假手术组、模型组和乌司他丁组,每组20只。采用盲肠结扎穿孔方法制备脓毒症大鼠模型,假手术组除不结扎和穿刺盲肠外,其余手术步骤相同,乌司他丁组小鼠术后30 min尾静脉给药100 000 U/kg。采用流式细胞仪检测各组小鼠CD4+CD25+Treg的凋亡率,采用酶联免疫吸附试验检测各组小鼠白细胞介素2(IL-2)、IL-4、干扰素γ的水平。

结果

假手术组、模型组和乌司他丁组小鼠CD4+CD25+Treg细胞的凋亡率比较,差异有统计学意义[(20.1 ± 1.0)%、(10.9 ± 0.8)%、(13.7 ± 0.8)%,F = 10.236,P = 0.030],且乌司他丁组小鼠显著低于假手术组,而高于模型组(P均< 0.05)。同时,与假手术组比较,模型组与乌司他丁组IL-2[(352 ± 76)、(172 ± 59)、(249 ± 64)ng/L]和干扰素γ[(177 ± 25)、(56 ± 14)、(109 ± 18)ng/L]均显著下降,而IL-4显著升高[(46 ± 15)、(328 ± 81)、(242 ± 62)ng/L],且与模型组比较,乌司他丁组IL-2和干扰素γ均明显升高,而IL-4明显降低(P均< 0.05)。

结论

乌司他丁可诱导脓毒症小鼠Treg细胞凋亡,上调IL-2和干扰素γ,降低IL-4水平。

Objective

To investigate the effect of ulinastatin on the apoptosis of regulatory T cells (Tregs) and cytokine secretion in septic mice.

Methods

A total of 60 male mice were randomized into the sham group, model group and ulinastatin group, 20 mice in each group. The model of sepsis was reproduced by cecal ligation and perforation, the mice in the sham group received celiotomy without ligation and puncture, and the mice in the ulinastatin group were given 100 000 U/kg ulinastatin by tail intravenous injection at 30 min after operation. The apoptosis rates of regulatory T cells were detected by flow cytometry, and the level of interleukin-2 (IL-2), IL-4 and interferon γ were determined by enzyme-linked immunosorbant assay.

Results

The apoptosis rates of Tregs in the sham group, model group and ulinastatin group showed significant differences [(20.1 ± 1.0)%, (10.9 ± 0.8)%, (13.7 ± 0.8)%, F = 10.236, P = 0.030], and the apoptosis rates of Tregs in the ulinastatin group were much lower than those in the sham group, and much higher than those in the model group (all P < 0.05). Meanwhile, the levels of IL-2 [(352 ± 76), (172 ± 59), (249 ± 64) ng/L] and interferon γ [(177 ± 25), (56 ± 14),(109 ± 18) ng/L] in the model group and ulinastatin group decreased obviously as compared with the sham group, and it decreased most in the model group (all P < 0.05). The levels of IL-4 in the model group and ulinastatin group were much higher than those in the sham group, and were highest in the model group [(46 ± 15), (328 ± 81), (242 ± 62) ng/L, all P < 0.05].

Conclusion

Ulinastatin may induce the apoptosis of Tregs, improve the levels of IL-2 and interferon γ, and reduce the levels of IL-4.

表1 各组小鼠CD4+CD25+Treg细胞的凋亡率( ± s
表2 各组小鼠细胞因子IL-2、IL-4及IFN-γ水平变化(ng/L, ± s
1
Unsinger J, McGlynn M, Kasten KR, et al. IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis[J]. J Immunol, 2010, 184 (7): 3768-3779.
2
Wan YY. Regulatory T cells: immune suppression and beyond[J]. Cell Mol Immunol, 2010, 7 (3): 204-210.
3
Sakaguchi S, Yamaguchi T, Nomura T, et al. Regulatory T cells and immune tolerance[J]. Cell, 2008, 133 (5): 775-787.
4
Cao C, Ma T, Chai YF, et al. The role of regulatory T cells in immune dysfunction during sepsis[J]. World J Emerg Med, 2015, 6 (1): 5-9.
5
Gadina M, O’Shea JJ. Immune modulation: Turncoat regulatory T cells[J]. Nat Med, 2009, 15 (12): 1365.
6
李国辉,马纪林,周红娟,等. 调节性T细胞及辅助性T细胞17在严重脓毒症患者中的表达及对预后影响[J/CD]. 中华危重症医学杂志(电子版),2014,7(6):377-381.
7
Suh HC, Benoukraf T, Shyamsunder P, et al. LPS independent activation of the pro-inflammatory receptor Trem1 by C/EBPε in granulocytes[J]. Sci Rep, 2017 (7): 46440.
8
Shimaoka M, Park EJ. Advances in understanding sepsis[J]. Eur J Anaesthesiol Suppl, 2008 (42): 146-153.
9
Venet F, Pachot A, Debard AL, et al. Increased percentage of CD4+CD25+ regulatory T cells during septic shock is due to the decrease of CD4+CD25- lymphocytes[J]. Crit Care Med, 2004, 32 (11): 2329-2331.
10
Sakaguchi S, Ono M, Setoguchi R, et al. Foxp3+CD25+CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease[J]. Immunol Rev, 2006 (212): 8-27.
11
Taylor AL, Llewelyn MJ. Superantigeninduced proliferation of human CD4+CD25-T cells is followed by a switch to a functional regulatory phenotype[J]. J Immunol, 2010, 185 (11): 6591-6598.
12
Nascimento DC, Alves-Filho JC, Sonego F, et al. Role of rugulatory T cells in long-term immune dysfunction associated with severe sepsis[J]. Crit Care Med, 2010, 38 (8): 1718-1725.
13
Rittirsch D, Huber-Lang MS, Flierl MA, et al. Immunodesign of experimental sepsis by cecal ligation and puncture[J]. Nat Protoc, 2009, 4 (1): 31-36.
14
吴铁军,张丽娜,亢翠翠. 乌司他丁对严重脓毒症患者炎症免疫失衡的调理作用[J]. 中华危重病急救医学,2013,25(4):219-223.
15
Chen X, Wang Y, Luo H, et al. Ulinastatin reduces urinary sepsis-related inflammation by upregulating IL-10 and downregulating TNF-α levels[J]. Mol Med Rep, 2013, 8 (1): 29-34.
16
Feng M, Shu Y, Yang Y, et al. Ulinastatin attenuates experimental autoimmune encephalomyelitis by enhancing anti-inflammatory responses[J]. Neurochem Int, 2014 (64): 64-72.
17
张莹,姚咏明,于燕,等. 高迁移率族蛋白B1对小鼠调节性T细胞与CD4+CD25-T细胞相互作用的影响[J]. 中华外科杂志,2008,46(3):217-220.
18
Hao X, Han J, Xing Z, et al. Urinary trypsin inhibitor attenuated inflammatory response of patients undergoing cardiopulmonary bypass by inducing activated Treg cells[J]. Inflammation, 2013, 36 (6): 1279-1285.
19
Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes[J]. Science, 2002, 298 (5594): 850-854.
20
Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival[J]. Nat Med, 2004, 10 (9): 942-949.
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