同种异体骨髓间充质干细胞移植治疗重症急性胰腺炎相关肺损伤

Transplantation of allogenetic bone marrow mesenchymal stem cells for treatment of severe acute pancreatitis induced lung injury in rats

背景:目前骨髓间充质干细胞移植治疗各种炎症性疾病研究甚多,但在重症急性胰腺炎相关器官损伤干预方面研究甚少。目的:观察同种异体骨髓间充质干细胞移植对重症急性胰腺炎相关肺损伤大鼠的干预作用。方法:采用全骨髓差异贴壁法培养获得骨髓间充质干细胞。100只SD大鼠随机取32只为假手术组,仅翻动轻柔胰腺;另68只制作重症急性胰腺炎肺损伤动物模型,并分为干预组和对照组,每组再分为4个时间点。分别经尾静脉注入1×109L-1浓度骨髓间充质干细胞悬液和同体积生理盐水。干预组每个时间点随机取1只注射CM-DiI标记的骨髓间充质干细胞悬液用于细胞示踪研究。结果与结论:逆行胆胰管注射建模能早期诱发重症急性胰腺炎及相关肺损伤,炎症因子及E-选择素表达明显增高,并且胰腺和肺的损伤程度随时间延长而加重;移植荧光标记的干细胞后肺组织可见红色荧光出现,并随时间增长而增多;干预组肺组织损伤情况均较对照组各时间点减轻,血清淀粉酶及炎症递质肿瘤坏死因子α、白细胞介素1β较对照组各时间点下降。干预组肺组织中E-选择素表达较对照组下降。提示同种异体骨髓间充质干细胞移植能有效保护肺血管内皮细胞,减轻重症急性胰腺炎相关肺损伤。

BACKGROUND：There are many studies describing transplantation of bone marrow mesenchymal stem cells for treatment of various inflammatory diseases.But few studies are reported on intervention of injury of organs related to severe acute pancreatitis.OBJECTIVE：To investigate the effect of allogenetic bone marrow mesenchymal stem cells transplantation on severe acute pancreatitis associated lung injury in rats.METHODS：Bone marrow mesenchymal stem cells were harvested by whole bone marrow adherence method.In the sham-operated group（n=32）,SD rats received only light and soft tipping of pancreatic gland.In the model group（n=68）,SD rats were prepared into severe acute pancreatitis models and randomly subdivided into an intervention subgroup and control subgroup.Four time points were designated for each subgroup.In the intervention subgroup,1×10 9 /L bone marrow mesenchymal stem cells suspension was injected via the tail vein;while in the control subgroup,equal amount of physiological saline was injected.In each subgroup,one rat per time point was selected for cell tracing by CM-Dil injection.RESULTS AND CONCLUSION：Retrograde cholangiopancereatography injection molding can induce severe acute pancreatitis and associated lung injury during the early stage.Inflammatory factor and E-selectin expression was significantly increased and pancreatic gland and lung injury was aggravated with prolonged time.After labeling,red fluorescence appeared in the lung tissue and increased with prolonged time.At each time point,lung injury was alleviated,serum amylase and tumor necrosis factor α and interleukin 1β expression was decreased in the intervention subgroup compared with the control subgroup.E-selectin expression in the intervention subgroup was significantly decreased than that in the control subgroup.Transplantation of allogenetic bone marrow mesenchymal stem cells can effectively alleviate severe acute pancreatitis associated lung injury.