首页|脐带间充质干细胞来源的膜联蛋白A1保护脂多糖诱导的急性肺损伤

脐带间充质干细胞来源的膜联蛋白A1保护脂多糖诱导的急性肺损伤

Annexin A1 derived from umbilical cord mesenchymal stem cells protects against lipopolysaccharide-induced acute lung injury

扫码查看
目的 探讨人脐带间充质干细胞(human umbilical cord mesenchymal stem cells,HucMSCs)来源的膜联蛋白 A1(annexin A1,ANXA1)对脂多糖(lipopolysaccharide,LPS)诱导的急性肺损伤(acute lung injury,ALI)的保护作用.方法 采用随机法将6周龄雄性C57BL/6小鼠分成5组,分别为假手术组、LPS组、LPS+HucMSC-cm(LPS+cm)组、LPS+nc-cm组和LPS+si-cm组,每组6只.通过向气管内注射LPS(5 mg/kg)建立ALI模型,LPS处理4 h后分别向气管内注射生理盐水、人脐带间充质干细胞上清(HucMSC conditioned medium,HucMSC-cm)、未敲除 ANXA1 的 HucMSC-cm(HucMSC-nc-cm)和敲除 ANXA1 的 HucMSC-cm(HucMSC-si-cm)各50 pL.LPS给药72 h后处死小鼠,留取血液及肺组织.采用酶联免疫吸附试验法检测小鼠外周血中白细胞介素6(interleukin-6,IL-6)的表达,采用苏木精伊红染色观察各组小鼠肺组织的病理学改变,Western blot和免疫组化法检测肺组织中炎症因子IL-6及血管细胞粘附分子-1(vascular cell adhesion molecule-1,VCAM-1)的表达.结果 相比于假手术组,LPS组小鼠肺组织炎性因子浸润明显增多,肺组织结构破坏,肺泡塌陷,肺组织损伤评分及肺湿干重比值(wet/dry weight ratio,W/D)增高(P<0.05),肺组织IL-6、VCAM-1蛋白水平表达增高(P<0.05),外周血中IL-6表达增加(P<0.05).而与LPS组相比,LPS+cm组小鼠肺组织病理损伤有所改善,肺组织损伤评分及肺W/D下降(P<0.05),肺组织中IL-6、VCAM-1蛋白水平表达及外周血中IL-6表达降低(P<0.05).LPS+cm组与LPS+nc-cm组相比差异无统计学意义(P>0.05).而LPS+si-cm组与LPS+nc-cm组相比,小鼠肺组织病理损伤再次加重,肺组织损伤评分及肺W/D同样上升(P<0.05),肺组织中IL-6、VCAM-1蛋白水平及外周血中IL-6表达再次增高(P<0.05).结论 来源于HucMSCs的ANXA1在LPS诱导的ALI模型中具有一定的保护作用.
Objective To investigate the protective effect of annexin A1(ANXA1)derived from human umbilical cord mesenchymal stem cells(HucMSCs)on lipopolysaccharide(LPS)-induced acute lung injury(ALI).Methods Six-week-old male C57BL/6 mice were randomly divided into a sham group,a LPS group,a LPS+HucMSC-cm(LPS+cm)group,a LPS+nc-cm group,and a LPS+si-cm group,with 6 mice in each group.LPS(5 mg/kg)was intratracheally injected to induce ALI model.Then,normal saline,HucMSC-cm(HucMSC conditioned medium),HucMSC-nc-cm(normal ANXA1 expression)and HucMSC-si-cm(knockout of ANXA1)were injected intratracheally with 50 pL each after LPS treatment for 4 hours.After 72 hours of LPS administration,the mice were killed,and the blood and lung tissues were retained.After corresponding treatment,the blood and lung tissues were preserved.The expression of IL-6 in peripheral blood of mice was detected by enzyme-linked immunosorbnent assay,the pathological changes of lung tissues were observed by hematoxylin-eosin staining,and the expressions of interleukin-6(IL-6)and vascular cell adhesion molecule-1(VCAM-1)in lung tissues of each group were detected by Western blot and immunohistochemistry.Results Compared with the sham group,the lung histopathology of mice in the LPS group showed significantly increased inflammatory factor infiltration,alveolar collapse,and lung tissue structure destruction as well as lung tissue injury score and wet/dry weight ratio(W/D)increased(all P<0.05).Accordingly,IL-6 and VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were increased(all P<0.05).Compared with the LPS group,the pathological injury of lung tissue in the LPS+cm group was improved,the lung tissue injury score and the W/D ratio decreased while IL-6,VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were decreased(all P<0.05).But there were no significant differences between the LPS+cm group and the LPS+nc-cm group(all P>0.05).Compared with the LPS+nc-cm group,lung tissue pathological injury was aggravated again,lung tissue injury score and W/D were also increased in the LPS+si-cm group(all P<0.05).IL-6 and VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were increased again(all P<0.05).Conclusion ANXA1 derived from HucMSCs has certain protective effect in LPS-induced ALI model.

Umbilical cord mesenchymal stem cellsAnnexin A1acute lung injuryinflammatory factor

陈海洋、彭肖康、杨宏锋、虞志新

展开 >

江苏大学附属人民医院重症医学科(江苏镇江 212002)

江苏大学医学院(江苏镇江 212013)

脐带间充质干细胞 膜联蛋白A1 急性肺损伤 炎症因子

江苏省自然科学基金

BK20160547

2024

中国呼吸与危重监护杂志
四川大学华西医学中心,四川大学华西医院

中国呼吸与危重监护杂志

CSTPCD
影响因子:1.306
ISSN:1671-6205
年,卷(期):2024.23(3)
  • 26