人脐带间充质干细胞防治新生大鼠急性肺损伤的作用

Effect of human umbilical cord mesenchymal stem cells on acute lung injury in newborn rats

背景:研究发现间充质干细胞对成年动物急性肺损伤具有一定的防治作用。目的:进一步验证人脐带间充质干细胞对内毒素所致的新生大鼠急性肺损伤的防治作用。方法:选取7 d龄新生SD大鼠120只,随机分为3组。模型组和干细胞组大鼠腹腔注射内毒素3 mg/kg建立新生鼠急性肺损伤模型;生理盐水组大鼠腹腔注射0.1 mL生理盐水。30 min后干细胞组腹腔注射0.1 mL人脐带间充质干细胞(1×106),生理盐水组和模型组大鼠腹腔注射等量生理盐水作对照。分别于6 h、1 d、2 d、4 d、7 d留取新生大鼠肺组织及血清标本,观察肺组织病理变化,ELISA方法测定血清中肿瘤坏死因子α及白细胞介素10的浓度及肺组织中髓过氧化物酶活性。结果与结论:肺组织苏木精-伊红染色及髓过氧化物酶活性均提示模型组呈急性肺损伤改变,干细胞组造模后4 d及7 d时肺损伤比模型组轻。与模型组比较,干细胞组的抗炎因子白细胞介素10水平显著升高,而促炎因子肿瘤坏死因子α则明显减低,差异有显著性意义(P<0.05)。说明用人脐带间充质干细胞早期细胞干预新生SD大鼠急性肺损伤,可以减轻肺部炎性病变,其主要机制可能为人脐带间充质干细胞通过免疫调节,平衡抗炎因子及促炎因子的表达,减轻肺损伤。

BACKGROUND：A series of studies have found that mesenchymal stem cells play an important role in the prevention and cure of acute lung injury in adult animals. OBJECTIVE：To further validate the effects of human umbilical cord mesenchymal stem cells on endotoxin-induced acute lung injury in newborn rats. METHODS：Total y 120 newborn rats aged 7 days were randomly assigned to three groups. Intraperitoneal injection of 3 mg/kg endotoxin was done to establish neonatal rat model of acute lung injury in the model and stem cellgroup. Rats in the normal saline group were intraperitoneal y injected with 0.1 mL normal saline. After 30 minutes of modeling, the rats in the stem cellgroup were subjected to intraperitoneal injection of 0.1 mL human umbilical cord mesenchymal stem cells （1×106）. The same volume of normal saline was administered in the normal saline and model groups. Lung tissue and blood specimens from newborn rats were taken at 6 hours, 1 day, 2 days, 4 days, and 7 days after treatment to observe lung pathological changes and detect levels of serum tumor necrosis factor-alpha and interleukin-10 as wel as myeloperoxidase activity in the lung tissue. RESULTS AND CONCLUSION：The lung hematoxylin-eosin staining and myeloperoxidase activity indicated acute lung injury in the model group. At 4 and 7 days after modeling, the severity of lung injury in the stem cellgroup was lighter than that in the model group. Compared with the model group, the interleukin-10 level was significantly increased in the stem cellgroup, while the level of tumor necrosis factor-alpha was significantly reduced （P〈0.05）. These findings suggest that human umbilical cord mesenchymal stem cells transplanted into newborn rats with acute lung injury can reduce lung inflammation, and the main mechanism may be that human umbilical cord mesenchymal stem cells can balance anti-inflammatory and pro-inflammatory factors and reduce lung injury through immune regulation.