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将原位胎儿肺组织直接注入肺部显示出对百草枯诱导的小鼠急性肺损伤具有预防作用。

Orthotopic foetal lung tissue direct injection into lung showed a preventive effect against paraquat-induced acute lung injury in mice.

作者信息

Okabe Ryo, Chen-Yoshikawa Toyofumi F, Yoshizawa Akihiko, Hirashima Tsuyoshi, Saito Masao, Date Hiroshi, Takebe Takanori

机构信息

Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Department of Thoracic Surgery, Graduate School of Medicine, Nagoya University, Nagoya, Japan.

出版信息

Eur J Cardiothorac Surg. 2020 Sep 1;58(3):638-645. doi: 10.1093/ejcts/ezaa091.

Abstract

OBJECTIVES

Lung transplantation is the only effective therapy for patients with end-stage lung disease but an organ shortage crisis necessitates the development of alternative therapies. Recent studies have highlighted the potential of foetal tissue transplantation to facilitate the regeneration of vital organs such as liver that have been damaged by lethal diseases. Herein, with the aim of restoring pulmonary function, we hypothesized that allogenic foetal lung tissue implantation would attenuate severe respiratory failure.

METHODS

Lung tissue from the foetuses of pregnant green fluorescent protein-C57BL/6 mice at 13.5 days of gestation was injected into the left lungs of recipient mice. Severe lung injury was induced by paraquat, and we analysed the survival rate and pathohistological findings after 1 month.

RESULTS

The survival rate of the therapy group was 39%, which was significantly higher than the vehicle group at 5.9% (P = 0.034). Immunochemical staining showed that positive cytoplasmic stained cells with anti-interleukin-10 antibody were identified in the gland-like structure of embryonic day 13.5 foetal lung. At 4 weeks after orthotopic implantation, haematoxylin and eosin staining showed reduced lung inflammatory cells, reduced lung oedema and increased active cell proliferation of foetal lung cells. Lung injury score showed that the airway septal thickening revealed statistically significant differences between vehicle and foetal lung therapy (P < 0.001).

CONCLUSIONS

Immature foetal lungs improved the survival rate of mice with paraquat-induced severe lung injury, establishing the need for systematic follow-up studies. The anti-inflammatory cytokine in the tissue from embryonic day 13.5 foetal lung might suppress severe lung injury.

摘要

目的

肺移植是终末期肺病患者唯一有效的治疗方法,但器官短缺危机促使人们开发替代疗法。最近的研究强调了胎儿组织移植在促进诸如因致命疾病而受损的肝脏等重要器官再生方面的潜力。在此,为了恢复肺功能,我们假设同种异体胎儿肺组织植入可减轻严重呼吸衰竭。

方法

将妊娠13.5天的绿色荧光蛋白-C57BL/6小鼠胎儿的肺组织注射到受体小鼠的左肺中。用百草枯诱导严重肺损伤,1个月后分析存活率和病理组织学结果。

结果

治疗组的存活率为39%,显著高于载体组的5.9%(P = 0.034)。免疫化学染色显示,用抗白细胞介素-10抗体进行细胞质阳性染色的细胞在胚胎第13.5天胎儿肺的腺样结构中被鉴定出来。原位植入4周后,苏木精和伊红染色显示肺部炎症细胞减少、肺水肿减轻以及胎儿肺细胞的活跃细胞增殖增加。肺损伤评分显示,载体组和胎儿肺治疗组之间气道间隔增厚存在统计学显著差异(P < 0.001)。

结论

未成熟胎儿肺提高了百草枯诱导的严重肺损伤小鼠的存活率,这表明有必要进行系统的随访研究。胚胎第13.5天胎儿肺组织中的抗炎细胞因子可能抑制严重肺损伤。

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