Heme oxygenase-1 modified mesenchymal stem cells in the treatment of ischemia-reperfusion injury in lung transplantation

Hong Junjie; Zhang Zhenyang; Lin Jiangbo; Kang Mingqiang; Yang Chuangcai; Peng Shuai; Zhuang Linwei; Lin Wenwei

doi:10.3760/cma.j.issn.1001-9030.2019.12.032

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• 实验研究 •

血红素加氧酶-1修饰间充质干细胞治疗肺移植缺血再灌注损伤的研究

中华实验外科杂志, 2019,36(12) : 2231-2233. DOI: 10.3760/cma.j.issn.1001-9030.2019.12.032

摘要

目的

探讨血红素加氧酶-1(HO-1)修饰间充质干细胞(MSCs)治疗肺移植缺血再灌注损伤(IRI)的保护机制。

方法

60只SD大鼠随机分为手术对照(Ⅰ)、单纯MSCs(Ⅱ)、空载体-MSCs(Ⅲ)，HO-1-MSCs(Ⅳ)，建立大鼠左肺原位移植模型，移植成功后Ⅱ、Ⅲ、Ⅳ组从受鼠肺动脉细针注入单纯MSCs、空载体-MSCs、HO-1-MSCs。4 h后测量氧分压(PaO₂)、二氧化碳分压(PaCO₂)、肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)含量、移植物湿/干比率(W/D)、超氧化物歧化酶(SOD)活性、丙二醛(MDA)和髓过氧化物酶(MPO)的含量；病理组织检测；反转录聚合酶链反应(RT-PCR)检测移植物中HO-1 mRNA的表达。多组间均数比较采用单因素方差分析。

结果

Ⅰ、Ⅱ、Ⅲ、Ⅳ组PaO₂[(70.40±4.64)、(87.53±4.01)、(87.27±4.06)、(96.80±6.47) mmHg(1 mmHg＝0.133 kPa)]逐渐升高(F＝75.578，P<0.01)，Ⅱ、Ⅲ组相当(F＝0.523，P>0.05)；Ⅰ、Ⅱ、Ⅲ、Ⅳ组PaCO₂[(32.67±3.31)、(27.80±2.98)、(27.60±2.41)、(19.87±3.02) mmHg]逐渐降低(F＝48.286，P<0.01)，Ⅱ、Ⅲ组相当(F＝0.480，P>0.05)；W/D：Ⅰ、Ⅱ、Ⅲ、Ⅳ组(4.96±0.22、4.04±0.28、4.11±0.31、3.85±0.27)逐渐降低(F＝48.992，P<0.01)，Ⅱ、Ⅲ组相当(F＝1.819，P>0.05)；Ⅰ、Ⅱ、Ⅲ、Ⅳ组MDA含量[(126.80±11.14)、(114.27±16.45)、(114.06±17.68)、(102.40±14.21) nmol/g]逐渐降低(F＝6.551，P<0.05)，Ⅱ、Ⅲ组相当(F＝0.638，P>0.05)；Ⅰ、Ⅱ、Ⅲ、Ⅳ组MPO含量[(53.51±3.06)、(45.07±3，32)、(44.45±3.37)、(40.60±2.47) U/g]逐渐降低(F＝46.907，P<0.01)，Ⅱ、Ⅲ组相当(F＝1.772，P>0.05)；SOD活性：Ⅰ、Ⅱ、Ⅲ、Ⅳ组[(304.60±34.74)、(329.87±19.44)、(329.87±19.44)、(338.73±15.77) U/g]逐渐升高(F＝6.038，P<0.01)，Ⅱ、Ⅲ组相当(F＝0.727，P>0.05)；Ⅰ、Ⅱ、Ⅲ、Ⅳ组TNF-α[(61.56±2.83)、(48.32±4.11)、(48.53±4.20)、(36.77±3.79) ng/L]逐渐降低(F＝108.215，P<0.01)，Ⅱ、Ⅲ组相当(F＝0.557，P>0.05)，Ⅰ、Ⅱ、Ⅲ、Ⅳ组IL-10[(23.43±2.37)、(34.96±3.04)、(35.48±3.00)、(41.16±3.12) ng/L]逐渐升高(F＝98.751，P<0.01)，Ⅱ、Ⅲ组相当(F＝0.437，P>0.05)。镜下见中性粒细胞浸润肺间质，肺泡腔内见炎性渗出，Ⅳ组炎症改变最轻；Ⅳ组出现明显的HO-1 mRNA扩增条带，强于其他组。

结论

HO-1修饰MSCs在治疗肺移植IRI中具有协同抗损伤作用。

引用本文: 洪俊杰, 张振阳, 林江波, 等. 血红素加氧酶-1修饰间充质干细胞治疗肺移植缺血再灌注损伤的研究 [J] . 中华实验外科杂志,2019,36 (12): 2231-2233. DOI: 10.3760/cma.j.issn.1001-9030.2019.12.032

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版权归中华医学会所有。

未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。

除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。

肺移植是肺源性疾病终末期的主要治疗手段，无心跳供体是当前最主要的供肺来源^[1,2]。血红素加氧酶-1(HO-1)修饰间充质干细胞(MSCs)已证实在改善心肌缺血、促进创面愈合和神经损伤修复等方面有较明显的效果，本研究旨在探讨HO-1-MSCs能否改善肺移植后缺血再灌注损伤(IRI)。

贡献者信息

洪俊杰

福建医科大学附属协和医院胸外二科，福州　350001

张振阳

福建医科大学附属协和医院胸外二科，福州　350001

林江波

福建医科大学附属协和医院胸外二科，福州　350001

康明强

福建医科大学附属协和医院胸外二科，福州　350001

杨创才

福建医科大学附属协和医院胸外二科，福州　350001

彭帅

福建医科大学附属协和医院胸外二科，福州　350001

庄林伟

福建医科大学附属协和医院胸外二科，福州　350001

林文伟

福建医科大学附属协和医院胸外二科，福州　350001

通信作者

林江波

福建医科大学附属协和医院胸外二科，福州　350001

Email：31368347@qq.com

关键词

血红素加氧酶-1; 间充质干细胞; 肺移植缺血再灌注损伤;

基金项目

福建省卫生厅中青年卫生骨干项目（2014-ZQN-JC-11）

作者声明

作者贡献声明　洪俊杰，杨创才，庄林伟负责实验操作、论文撰写；彭帅，林文伟负责数据统计分析；林江波，康明强，张振阳负责实验指导；洪俊杰与张振阳对本文有同等贡献

利益冲突

利益冲突　所有作者均声明不存在利益冲突

历史

出版日期：2019-12-08

收稿日期：2019-06-21

Experimental Study

Heme oxygenase-1 modified mesenchymal stem cells in the treatment of ischemia-reperfusion injury in lung transplantation

Hong Junjie, Zhang Zhenyang, Lin Jiangbo, Kang Mingqiang, Yang Chuangcai, Peng Shuai, Zhuang Linwei, Lin Wenwei

Published 2019-12-08

Cite as Chin J Exp Surg, 2019,36(12): 2231-2233. DOI: 10.3760/cma.j.issn.1001-9030.2019.12.032

Abstract

Objective

To explore the protective mechanism of Heme Oxygenase-1 (HO-1) modified mesenchymal stem cells (MSC) in the treatment of lung transplantation ischemia-reperfusion injury (IRI).

Methods

Sixty SD rats were randomly divided into Surgical control (Ⅰ), simple MSCs (Ⅱ), empty vector-MSCs (Ⅲ), HO-1 modified MSCs (Ⅳ) were established. After establishing orthotopic left lung transplantation model in rats, group Ⅱ, Ⅲ and Ⅳ were injected with MSCs, empty vector-MSCs and HO-1-MSCs from pulmonary artery fine needles of recipient rats. Four hours later, partial pressure of oxygen (PaO₂), partial pressure of carbon dioxide (PaCO₂), tumor necrosis factor-alpha (TNF-α), Interleukin-10 (IL-10), wet/dry ratio (W/D), superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO) were measured. Histopathological examination. Detection of HO-1-mRNA expression in transplants by reverse transcription polymerase chain reaction (RT-PCR). Multigroup mean comparison using One-way ANOVA.

Results

PaO₂: Group Ⅰ, Ⅱ, Ⅲ and Ⅳ were (70.40±4.64), (87.53±4.01), (87.27±4.06), (96.80±647) mmHg (1 mmHg=0.133 kPa) gradually increased (F=75.578, P<0.01). Group II and III were similar (F=0.523, P>0.05). PaCO₂: group Ⅰ, Ⅱ, Ⅲ and Ⅳ were (32.67±3.31), (27.80±2.98), (27.60±2.41), (19.87±3.02) mmHg gradually decreased (F=48.286, P<0.01), group Ⅱ and Ⅲ were similar (F=0.480, P>0.05). W/D: Group Ⅰ, Ⅱ, Ⅲ and Ⅳ were (4.96±0.22), (4.04±0.28), (4.11±0.31), (3.85±0.27) gradually decreased (F=48.992, P<0.01), group Ⅱ and Ⅲ were similar (F=1.819, P>0.05). MDA content: In group Ⅰ, Ⅱ, Ⅲ and Ⅳ, the levels of MDA were (126.80±11.14), (114.27±16.45), (114.06±17.68), (102.40±14.21) nmol/g gradually decreased (F=6.551, P<0.05), group Ⅱ and Ⅲ were similar (F=0.638, P>0.05). MPO content: group Ⅰ, Ⅱ, Ⅲ and Ⅳ were (53.51±3.06), (45.07±3, 32), (44.45±3.37), (40.60±2.47) U/g decreased gradually (F=46.907, P<0.01), group Ⅱ and Ⅲ were similar (F=1.772, P>0.05). SOD activity: In group Ⅰ, Ⅱ, Ⅲ and Ⅳ, SOD activity increased gradually [(304.60±34.74), (329.87±19.44), (329.87±19.44), (338.73±15.77) U/g, (F=6.038, P<0.01], while in group Ⅱ and Ⅲ, it was the same (F=0.727, P>0.05). TNF-α: In group Ⅰ, Ⅱ, Ⅲ and Ⅳ, the levels of TNF-αwere (61.56±2.83), (48.32±4.11), (48.53±4.20), (36.77±3.79) ng/L gradually decreased (F=108.215, P<0.01), group Ⅱ and group Ⅲ were similar (F=0.557, P>0.05). IL-10: The levels of IL-10 in group Ⅰ, Ⅱ, Ⅲ and Ⅳ were (23.43±2.37), (34.96±3.04), (35.48±3.00), (41.16±3.12) ng/L gradually increased (F=98.751, P<0.01). In group II and group III, the levels were similar (F=0.437, P>0.05). Under light microscopy, neutrophils infiltrated pulmonary interstitium and inflammatory exudation was seen in alveolar cavity. Inflammation in group Ⅳ was the lightest in each group. The amplification bands of HO-1 mRNA in group IV were significantly stronger than other groups.

Conclusion

HO-1 gene modified MSCs have synergistic anti-injury effect in the treatment of lung transplantation IRI.

Key words:

Heme oxygenase-1; Mesenchymal stem cells; Lung transplantation ischemia-reperfusion injury

Contributor Information

Hong Junjie

Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China

Zhang Zhenyang

Lin Jiangbo

Kang Mingqiang

Yang Chuangcai

Peng Shuai

Zhuang Linwei

Lin Wenwei

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