Bone marrow-derived mesenchymal stromal cells ameliorate severe acute pancreatitis in rats via hemeoxygenase-1-mediated anti-oxidant and anti-inflammatory effects

被引:33
作者
Ma, Zhilong [1 ]
Song, Guodong [1 ,2 ]
Zhao, Dongbo [1 ,2 ]
Liu, Dalu [1 ,3 ]
Liu, Xiaolei [1 ]
Dai, Yuxiang [1 ]
He, Zhigang [1 ]
Qian, Daohai [4 ]
Gong, Jian [1 ]
Meng, Hongbo [1 ]
Zhou, Bo [1 ]
Yang, Tingsong [1 ]
Song, Zhenshun [1 ]
机构
[1] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gen Surg, Shanghai, Peoples R China
[2] Nanjing Med Univ, Clin Med Coll, Nanjing, Jiangsu, Peoples R China
[3] Anhui Med Univ, Shanghai Clin Med Coll, Hefei, Anhui, Peoples R China
[4] Yijishan Hosp, Wannan Med Coll, Dept Hepatobiliary Surg, Wuhu, Anhui, Peoples R China
基金
中国国家自然科学基金;
关键词
heme oxygenase-1; inflammatory; mesenchymal stromal cells; oxidative stress; severe acute pancreatitis; HEME OXYGENASE-1 EXPRESSION; STEM-CELLS; INDUCTION; MACROPHAGES; PROTECTS; IMPROVES; GENE; SITE; MICE;
D O I
10.1016/j.jcyt.2018.11.013
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Background and aims: It has been previously verified that mesenchymal stromal cells (MSCs) have a good therapeutic effect on severe acute pancreatitis (SAP) and the potential for regeneration of damaged pancreatic tissue, but the exact molecular mechanism remains unclear. In this study, we demonstrated the therapeutic effect of bone morrow MSCs (BMSCs) on SAP, probably by targeting heme oxygenase-1 (HO-1). Methods: Six hours after SAP induction, either phosphate-buffered saline (PBS) or BMSCs were transfused into the caudal vein of rats, zinc protoporphyrin (ZnPP) was administered intraperitoneally. Pancreatic pathological scoring, serum levels of amylase and inflammatory factors, as well as levels of reactive oxygen species (ROS), malondialdehyde (MDA) and myeloperoxidase (MPO), superoxide dismutase (SOD) and catalase (CAT) activity in the pancreas were evaluated. Results: Our data showed that BMSCs significantly reduce inflammation and oxidative stress, reduce apoptosis and promote angiogenesis of damaged pancreas. Moreover, BMSCs increased the level of HO-1 in the serum and pancreatic tissue in rats with SAP. In addition, the protective effect of BMSCs was partially neutralized by the HO-1 activity inhibitor ZnPP, suggesting a key role of HO-1 in the therapeutic effect of BMSCs on SAP. Conclusions: BMSCs ameliorated SAP, probably by inducing expression of HO-1, which can exert anti-inflammatory and antioxidant effects, reduce apoptosis and promote angiogenesis.
引用
收藏
页码:162 / 174
页数:13
相关论文
共 45 条
[1]  
Aziz N M, 2017, Endocr Regul, V51, P20, DOI 10.1515/enr-2017-0003
[2]   Induction of heme oxygenase-1 improves the survival of pancreas grafts by prevention of pancreatitis after transplantation [J].
Becker, Thomas ;
Vilsendorf, Andreas Meyer zu ;
Terbish, Talvankhuu ;
Klempnauer, Jurgen ;
Joerns, Anne .
TRANSPLANTATION, 2007, 84 (12) :1644-1655
[3]   IAP/APA evidence-based guidelines for the management of acute pancreatitis [J].
Besselink, Marc ;
van Santvoort, Hjalmar ;
Freeman, Martin ;
Gardner, Timothy ;
Mayerle, Julia ;
Vege, Santhi Swaroop ;
Werner, Jens ;
Banks, Peter ;
McKay, Colin ;
Fernandez-del Castillo, Carlos ;
French, Jeremy ;
Gooszen, Hein ;
Johnson, Colin ;
Sarr, Mike ;
Takada, Tadahiro ;
Windsor, John ;
Saluja, Ashok ;
Liddle, Rodger ;
Papachristou, Georgios ;
Singh, Vijay ;
Ruenzi, Michael ;
Wu, Bechien ;
Singh, Vikesh ;
Bollen, Thomas ;
Morgan, Desiree ;
Mortele, Koenraad ;
Mittal, Anubhav ;
En-qiang, Mao ;
de Waele, Jan ;
Petrov, Maxim ;
Dellinger, Patchen ;
Lerch, Markus M. ;
Anderson, Roland ;
McClave, Stephen ;
Hartwig, Werner ;
Bruno, Marco ;
Oria, Alejandro ;
Baron, Todd ;
Fagenholz, Peter ;
Horvath, Karen ;
van Baal, Mark ;
Nealon, William ;
Andren-Sandberg, Ake ;
Bakker, Olaf ;
Bassi, Claudio ;
Buchler, Markus ;
Boermeester, Marja ;
Bradley, Ed ;
Chari, Suresh ;
Charnley, Richard .
PANCREATOLOGY, 2013, 13 (04) :E1-E15
[4]   Inducers of heme oxygenase-1 [J].
Ferrandiz, M. L. ;
Devesa, I. .
CURRENT PHARMACEUTICAL DESIGN, 2008, 14 (05) :473-486
[5]   The SDF-1/CXCR4 axis regulates migration of transplanted bone marrow mesenchymal stem cells towards the pancreas in rats with acute pancreatitis [J].
Gong, Jian ;
Meng, Hong-Bo ;
Hua, Jie ;
Song, Zhen-Shun ;
He, Zhi-Gang ;
Zhou, Bo ;
Qian, Ming-Ping .
MOLECULAR MEDICINE REPORTS, 2014, 9 (05) :1575-1582
[6]   Acute pancreatitis: Models, markers, and mediators [J].
Granger, J ;
Remick, D .
SHOCK, 2005, 24 :45-51
[7]   Clinical practice guideline: management of acute pancreatitis [J].
Greenberg, Joshua A. ;
Hsu, Jonathan ;
Bawazeer, Mohammad ;
Marshall, John ;
Friedrich, Jan O. ;
Nathens, Avery ;
Coburn, Natalie ;
May, Gary R. ;
Pearsall, Emily ;
McLeod, Robin S. .
CANADIAN JOURNAL OF SURGERY, 2016, 59 (02) :128-140
[8]   Panhematin provides a therapeutic benefit in experimental pancreatitis [J].
Habtezion, Aida ;
Kwan, Raymond ;
Akhtar, Ehsaan ;
Wanaski, Stephen P. ;
Collins, Stephen D. ;
Wong, Ronald J. ;
Stevenson, David K. ;
Butcher, Eugene C. ;
Omary, M. Bishr .
GUT, 2011, 60 (05) :671-679
[9]   Celecoxib activates PI-3K/Akt and mitochondrial redox signaling to enhance heme oxygenase-1-mediated anti-inflammatory activity in vascular endothelium [J].
Hamdulay, Shahir S. ;
Wang, Bufei ;
Birdsey, Graeme M. ;
Ali, Faisal ;
Dumont, Odile ;
Evans, Paul C. ;
Haskard, Dorian O. ;
Wheeler-Jones, Caroline P. ;
Mason, Justin C. .
FREE RADICAL BIOLOGY AND MEDICINE, 2010, 48 (08) :1013-1023
[10]  
He Z, 2016, SCI REP-UK, V6, P6