Role of bone marrow mesenchymal stem cells in L-arg-induced acute pancreatitis: effects and possible mechanisms.
Role of bone marrow mesenchymal stem cells in L-arg-induced acute pancreatitis: effects and possible mechanisms.
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发表时间：
2015-05
影响因子：
1.4
通讯作者：
Guojian Yin;Guoyong Hu;Rong Wan;Ge Yu;Xiaofeng Cang;Jianbo Ni;J. Xiong;Y. Hu;M. Xing;Y. Fan;W. Xiao;Lei Qiu;Shaofeng Wang;Xingpeng Wang
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作者：
Guojian Yin;Guoyong Hu;Rong Wan;Ge Yu;Xiaofeng Cang;Jianbo Ni;J. Xiong;Y. Hu;M. Xing;Y. Fan;W. Xiao;Lei Qiu;Shaofeng Wang;Xingpeng Wang
骨髓间充质干细胞（MSC）对全身炎症具有明显的保护作用。本研究旨在探讨骨髓间充质干细胞（bmMSCs）对急性胰腺炎（AP）的治疗作用及其可能机制。方法体外分离培养SD大鼠骨髓间充质干细胞。采用L-精氨酸诱导的急性胰腺炎模型。通过血清淀粉酶、脂肪酶、细胞因子和胰腺组织学检查评估胰腺损伤。RT-PCR检测胰腺组织中mRNA的表达。采用Western-blot和免疫组化方法检测NF-κB p65信号通路的作用。对CM-Dil标记的骨髓间充质干细胞进行体内示踪定位研究。结果bmMSCs可明显减轻急性胰腺损伤和AP相关肺损伤，降低血清IL-1β、IL-6、TNF-α水平，下调胰腺组织IL-1α、IL-6、TNF-α表达，减少NF-κB p65核转位。在AP的早期阶段，骨髓间充质干细胞在体内的定位是由于被动地被困在相关器官中，而不是主动地归巢到胰腺的炎症部位。结论bmMSCs对AP具有多方面的保护作用，其机制可能与通过外分泌调节炎性细胞因子的释放有关。
OBJECTIVES Mesenchymal stem cells (MSCs) have shown an obvious protective effect on systemic inflammation. The purpose of this study is to assess the effect and possible mechanism of bone marrow MSCs (bmMSCs) on acute pancreatitis (AP). METHODS BmMSCs of SD rats were isolated and cultured in vitro. L-Arginine-induced acute pancreatitis was used as AP model in vivo. Pancreatic injury was assessed by serum amylase, lipase, cytokines and pancreatic histology. RT-PCR was applied to investigate mRNA expression of pancreas tissue. Western-blot and immunohistochemistry (IHC) were applied to test the role of NF-κB p65 signaling pathway. Tracking and Positioning of CM-Dil labeled bmMSCs in vivo was further studied. RESULTS Treatment with bmMSCs attenuated acute pancreatic injury and AP-associated lung injury obviously, with decreased serum IL-1β, IL-6, TNF-α, down-regulated expressions of IL-1α, IL-6, TNFα in pancreas tissue and reduced nuclear translocation of NF-κB p65 in AP. Localization of bmMSCs in vivo was due to being passively trapped in related organs, but not actively homing to inflammatory sites of pancreas during the early phase of AP. CONCLUSIONS Taken together, the results showed that bmMSCs played a protective role in AP in many aspects, which might protect against experimental pancreatitis partly by regulating release of inflammatory cytokines by an exocrine secretion.