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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2020, Vol. 13 ›› Issue (03) : 340 -344. doi: 10.3877/cma.j.issn.1674-6902.2020.03.010

论著

NIX在机械牵张诱导的急性肺损伤中的表达及其严重程度的相关性
赖志远1, 刘振玉1,†(), 李修江1, 周强平1   
  1. 1. 330006　江西，南昌大学第一附属医院急诊创伤抢救中心
  • 收稿日期:2019-01-21 出版日期:2020-06-25
  • 通信作者: 刘振玉
  • 基金资助:
    江西省教育厅课题(170044)

Expression of Nix after mechanical stretch-induced acute lung injury and its correlation with injury severity

Zhiyuan Lai1, Zhenyu Liu1,†(), Xiujiang Li1, Qiangping Zhou1   

  1. 1. Emergency Trauma Rescue Center, First Affiliated Hospital, Nanchang University, Nanchang 330006, China
  • Received:2019-01-21 Published:2020-06-25
  • Corresponding author: Zhenyu Liu
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引用本文：

赖志远, 刘振玉, 李修江, 周强平. NIX在机械牵张诱导的急性肺损伤中的表达及其严重程度的相关性[J/OL]. 中华肺部疾病杂志(电子版), 2020, 13(03): 340-344.

Zhiyuan Lai, Zhenyu Liu, Xiujiang Li, Qiangping Zhou. Expression of Nix after mechanical stretch-induced acute lung injury and its correlation with injury severity[J/OL]. Chinese Journal of Lung Diseases(Electronic Edition), 2020, 13(03): 340-344.

目的

急性肺损伤的本质是各种内外因素引起的全身失控性炎症反应，胸部撞击伤是急性肺损伤的常见原因之一。Nix作为Bcl-2的家族成员，研究发现，Nix在多种人组织细胞的凋亡途径中发挥着重要的作用。本研究旨在探讨NIX在机械牵张诱导的急性肺损伤中的表达及其严重程度的相关性；

方法

小生物撞击仪器精准控制建立不同严重程度大鼠胸部撞击伤模型，分组轻伤、重伤、严重伤组，对照组(n＝10)不做处理；各模型组(n＝10)分别于精准撞击后0.5、2、12、24、48、72 h后无伤取其肺组织，利用HE染色观察其病理学变化。取不同损伤程度的AT-Ⅱ型细胞培养株，RT-PCR技术检测各模型组各个时间点肺泡细胞Nix的表达情况，Western blot检测蛋白表达情况。

结果

撞击伤大鼠模型组肺组织出现不同程度的出血、水肿并大量炎性细胞浸润。与对照组相比，在撞击0.5、2、12、24、48、72 h后，各模型组大鼠肺组织中Nix mRNA都存在较为明显增高，Nix mRNA在伤后0.5 h已经开始增高，并在撞击48 h后Nix mRNA的表达达到峰值，撞击伤后72 h已有显著下降(P<0.05)，接近伤后0.5 h水平，并随着撞击伤的严重程度Nix mRNA表达水平也呈相应的增高(P<0.05)。与对照组相比，各模型组大鼠肺组织Nix蛋白表达水平也与Nix mRNA表达水平呈现相同的变化曲线(P<0.05)，且同样随撞击伤严重程度的增高而增高(P<0.05)。

结论

在机械牵张诱导的急性肺损伤中，肺组织中Nix基因的表达情况与肺损伤严重程度呈正相关(P<0.05)。这为我们通过Nix作为靶点进行肺组织相关疾病的研究提供理论依据。

关键词: 急性肺损伤, Nix, 机械牵张, 胸部撞击伤
Objective

To investigate the correlation between the expression and injury severity of Nix after acute lung injury induced by mechanical stretch.

Methods

A small biological impact instrument accurately controlled the establishment of rat chest impact injury models with different injury severities: 10 rats with minor injury (the minor injury group), 10 with moderate injury (the moderate injury group), and 10 with serious injury (the serious injury group). And 10 rats received no treatment as the control group. Then lung tissues of all the groups were taken with no injury 0.5, 2, 12, 24, 48, and 72 h after the precise impact, respectively, and HE staining was employed to observe the pathological changes. The AT-Ⅱ cell culture strains with different degrees of injury were taken and RT-PCR was used to detect the expression of Nix in the alveolar cells at each time point. The expression levels of proteins were detected by Western blotting method.

Results

The lung tissues of the injury groups showed different degrees of hemorrhage, edema and massive inflammatory cell infiltration. Compared with the control group, after the impact for 0.5, 2, 12, 24, 48, and 72 h, the expression of Nix mRNA in the lung tissues of each injury group was significantly increased, and Nix mRNA expression began to increase 0.5 h after injury. The expression of Nix mRNA peaked at 48 h after impact, and decreased significantly at 72 h after impact (P<0.05), which was close to that of 0.5 h after injury. And the expression levels of Nix mRNA increased correspondingly with the severity of impact injury (P<0.05). Compared with the control group, the expression of Nix proteins in the lung tissues of each injury group also showed the same change curve with the expression level of Nix mRNA (P<0.05), and also increased with the severity of impact injury (P<0.05).

Conclusion

In the rats with acute lung injury induced by mechanical stretch, the expression of Nix gene in the lung tissues was positively correlated with the severity of lung injury (P<0.05). This provides a theoretical basis for our study on lung tissue-related diseases through Nix as a target.

Key words: Acute lung injury, Nix, Mechanical stretch, Chest impact injury
图1 撞击伤后48 h大鼠肺组织病理学变化情况
图2 免疫组化、Western Blot和RT-PCR检测；注：A：免疫组化法检测Nix在致伤组肺组织中的表达(SP法，DAB显色，×400); B：RT-PCR检测Nix mRNA表达情况；C：Western Blot检测Nix蛋白的表达情况
表1 Nix mRNA表达情况与肺组织损伤程度的关系(n＝10，±s)
组　别 0.5 h 2 h 12 h 24 h 48 h 72 h
对照组 0.051±0.0046 0.051±0.0054 0.051±0.0073 0.051±0.0062 0.051±0.0046 0.051±0.0082
轻伤 0.368±0.072 0.487±0.083 0.652±0.098 0.691±0.096 0.952±0.082 0.342±0.043
重伤 0.569±0.071 0.673±0.064 0.752±0.091 0.891±0.099 1.491±0.072 0.300±0.051
严重伤 0.638±0.072 0.885±0.072 0.922±0.063 0.998±0.098 2.658±0.092 0.640±0.052
表2 Nix蛋白表达情况与肺组织损伤程度的关系(n＝10，±s)
组　别 0.5 h 2 h 12 h 24 h 48 h 72 h
对照组 0.051±0.0036 0.051±0.0046 0.051±0.0146 0.051±0.0056 0.051±0.0066 0.051±0.0046
轻伤 0.361±0.072 0.487±0.083 0.652±0.091 0.691±0.093 1.111±0.082 0.342±0.043
重伤 0.360±0.072 0.492±0.073 0.699±0.094 0.721±0.096 1.562±0.062 0.396±0.049
严重伤 0.378±0.072 0.527±0.094 0.752±0.088 0.891±0.067 1.990±0.033 0.540±0.072
1
蒋耀光. 胸部创伤诊治的进展[J]. 创伤外科杂志，2003, 5(5): 321-324.
2
王海燕，杜　娟，赵玉金，等. 胸部撞击伤复合脂多糖致急性肺损伤大鼠模型的建立[J]. 创伤外科杂志，2014, 16(1): 46-49.
3
Huang X, Magnotti LJ, Fabian TC, et al. Does lack of thoracic trauma attenuate the severity of pulmonary failure? An 8-year analysis of critically injured patients[J]. Eur J Trauma Emerg Surg, 2020, 46(1): 3-9.
4
雷元辉. 重症胸部创伤并发ARDS疾病患者施行保护性肺通气疗法的效果研究[J]. 世界最新医学信息文摘，2017, 17(74): 4-5, 13.
5
王　薇. 保护性肺通气治疗重症胸部创伤合并急性呼吸窘迫综合征的疗效分析[J]. 浙江创伤外科，2016, 21(4): 761-763.
6
Luh SP, Chiang CH. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism, present strategies and future perspectives of therapies [J]. J Zhejiang Univ Sci B, 2007, 8(1): 60-69.
7
尹　文，刘　健，黄　扬，等. 急性肺损伤发病机制和治疗现状[J]. 中国急救医学，2008, 28(9): 840-842.
8
Vito Fanelli, Marco Ranieri V. Mechanisms and clinical consequences of acute lung injury[J]. Ann Am Thorac Soc, 2015, 12 Suppl 1：S3-8.
9
黄　一，王婷婷，游　凯，等. NIX介导的细胞自噬在低氧诱导ATⅡ凋亡中的作用[J]. 西南国防医药，2015, 25(8): 847-850.
10
廖克龙，朱佩芳，王正国，等. 大鼠胸部撞击伤肺损伤模型的建立[J]. 创伤外科杂志，2001, 3(4): 263-265.
11
赖志远，刘振玉，李修江，等. NIX基因在机械牵张诱导肺组织损伤中的作用[J]. 江西医药，2019, 54(9): 1021-1025，1036.
12
韩医峰. 肺保护性通气在严重胸部创伤并发急性呼吸窘迫综合征中的应用[J]. 现代诊断与治疗，2018, 29(21): 3488-3489.
13
Andrew MJ. Management of post traumatic respiratory failure[J]. Crit Care Clin, 2004, 20(1): 83-99.
14
Kiraly L, Schreiber M. Management of the crushed chest[J]. Crit Care Med, 2010, 38(9): S469-477.
15
Jain M, Sznajder JI. Effects of hypoxia on the alveolar epithelium[J]. Proc Am Thorac Soc, 2005, 2(3): 202-205.
16
Krick S, Eul BG, Hanze J, et al. Role of hypoxia-inducible factor-1alpha in hypoxia-induced apoptosis of primary alveolar epithelial type Ⅱ cells[J]. Am J Respir Cell Mol Biol, 2005, 32(5): 395-403.
17
Ma JL, Ni HB, Rui Q, et al. Potential Roles of NIX/BNIP3L Pathway in Rat Traumatic Brain Injury[J]. Cell Transplant, 2019, 28(5): 585-595.
18
袁长青，丁振华. Caspase的活化及其在细胞凋亡中的作用[J]. 生理科学进展，2002, 33(3): 220-224.
19
Bratton SB, MacFarlane M, Cain K , et al. Protein complex es activate distinct caspase cascades in death receptor and stress-induced apo ptosis[J]. Exp Cell Res, 2000, 256(1): 27-33.
20
袁建平，王洪涛，赵　蔚，等. 柯萨奇病毒B3通过Caspase依赖途径诱导HeLa细胞凋亡[J]. 细胞与分子免疫学杂志，2001, 17(5): 424-425，436.
21
Zhang J, Ney PA. Role of BNIP3 and NIX in cell death, autophagy，and mitophagy[J]. Cell Death Differ, 2009, 16(7): 939- 946.
22
Koyama AH, Fukumori T, Fujita M, et al. Physiological significance of apoptosis in animal virus infection[J]. Microbes and Infection, 2000, 2(9): 1111-1117.
23
Ma JL, Ni HB, Rui Q, et al. Potential Roles of NIX/BNIP3L Pathway in Rat Traumatic Brain Injury[J]. Cell transplant, 2019, 28(5): 585-595.
24
Mcdonnell LK, Hume PA, Nolte V. Rib stress fractures among rowers definition, epidemiology, mechanisms, risk factors and effectiveness of injury prevention strategies[J]. Sports Medicine, 2011, 41(11): 883-901.
25
Shen J, Chen X, Li H, et al. p75 neurotrophin receptor and its novel interaction partner, NIX, are involved in neuronal apoptosis after intracerebral hemorrhage[J]. Cell Tissue Res, 2017, 368(1): 13-27.
26
McLelland Gian-Luca, Soubannier Vincent, Chen Carol X, et al. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control[J]. The EMBO J, 2014, 33(4): 282-295.
27
O′Sullivan Timothy E, Johnson Lexus R, Kang Helen H, et al. BNIP3- and BNIP3L-Mediated Mitophagy Promotes the Generation of Natural Killer Cell Memory[J]. Immunity, 2015, 43(2): 331-342.
28
Gao F, Chen D, Si JM, et al. The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy in PINK1/PARK2 pathway[J]. Hum Mol Genet, 2015, 24(9): 2528-2538.
29
Roperto Sante, De Falco Francesca, Perillo Antonella. Mitophagy mediated by BNIP3 and BNIP3L/NIX in urothelial cells of the urinary bladder of cattle harbouring bovine papillomavirus infection[J]. Vet Microbiol, 2019, 236: 108396.
30
Subbiah R, Dhamotharan P, Rajaguru P, et al. MicroRNA Regulation of Acute Lung Injury and Acute Respiratory Distress Syndrome[J]. J Cell Physiol, 2016, 231(10): 2097-2106.
31
Xu XP, Huang LL, Hu SL, et al. Genetic Modification of Mesenchymal Stem Cells Overexpressing Angiotensin Ⅱ Type 2 Receptor Increases Cell Migration to Injured Lung in LPS-Induced Acute Lung Injury Mice[J]. Stem Cells Transl Med, 2018, 7(10): 721-730.
32
Zhang J, Ney PA. Role of BNIP3 and NIX in cell death, autophagy，and mitophagy [J]. Cell Death Differ, 2009, 16(7): 939-946.
33
Abhinav D, Scot JM, Yuan Qy, et al. Endoplasmic reticulum-mitochondria crosstalk in NIX-mediated murine cell death[J]. J Clin Invest, 2009, 119(1): 203-212.
34
江林敏，熊　彬，李　多. 低氧诱导因子1α在急性肺损伤发病机制中的研究进展[J]. 现代临床医学，2018, 44(5): 391-393.
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