Chinese Journal of General Surgery ›› 2021, Vol. 30 ›› Issue (3): 294-304.doi: 10.7659/j.issn.1005-6947.2021.03.007

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Anti-inflammatory effect of bone marrow mesenchymal stem cells in rats with severe acute pancreatitis and its association with TLR4/NF-κBp65 pathway

QIN Yafei1, HUO Xingguang2, LI Qiuxia1, XU Yusheng3   

  1. (1. Department of Critical Care Medicine, Zhoukou Orthopedic Hospital, Zhoukou, Henan 466000, China; 2. the Second Public Health Supervision Division of Zhoukou Health and Family Planning Supervision Bureau, Zhoukou, Henan 466000, China; 3. Department of Orthopedics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China)
  • Received:2020-09-23 Revised:2021-02-17 Online:2021-03-25 Published:2021-04-06

Abstract: Background and Aims: Severe acute pancreatitis (SAP) is one of the most frequently encountered serious acute illnesses in clinical practice. Inflammation plays an important role in its occurrence and development. At present, bone marrow mesenchymal stem cell (MSC) transplantation is considered having the potential to repair the pancreatic tissue injury caused by SAP, but the specific function is unclear. Therefore, this study was conducted to explore the anti-inflammatory effect of bone marrow MSC and its mechanism in SAP using SAP rat models. 
Methods: The bone marrow MSCs were isolated from the SD rats, and then were cultured and identified, and finally prepared into cell suspension with a density of 1.0×106/mL. Rat SAP models were created by retrograde injection of 3.5% sodium deoxycholate into the biliopancreatic duct. Thirty-six SD rats with successful model induction were randomly divided in four groups, and underwent intraperitoneal injection of normal saline (model group), intraperitoneal injection of MSC suspension (intraperitoneal injection group), tail vein injection of MSC suspension (tail vein injection group), or intraperitoneal injection plus tail vein injection of MSC suspension (combined injection group) at 12 h after modeling, respectively. In addition, another 9 SD rats underwent sham operation (sham operation group), and then received intraperitoneal injection of normal saline of the same volume 12 h after operation. The rats in each group were sacrificed 24 h after injection and the blood and pancreatic tissue samples were harvested. The pathological changes of pancreatic tissue were observed and the degrees of pancreatic damage were scored. The serum levels of amylase (AMS) and lipase (LPS) were measured by iodine colorimetry and methyl halide substrate methods respectively. The contents of IL-6, IL-1β and TNF-α in pancreatic tissue were detected by ELISA assay. The activity of peroxidase (SOD) was detected by hydroxylamine method, and concentration of malondialdehyde (MDA) was detected by thiobarbituric acid method. The mRNA expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), NF-κBp65 were determined by RT-PCR, and the protein expressions of TLR4, MyD88, and NF-κBp65 were examined by Western blot.
Results: The MSCs were spindle-shaped and formed whirlpool-like patterns, with low CD45 expression (1.25%) and high CD90 expression (99.89%) as well as good viability. Compared with sham operation group, in all other groups, the pancreatic tissues showed varying degrees of damage, the serum levels of AMS and LPS, and the pancreatic contents of IL-6, IL-1β, TNF-α and MDA were significantly increased, while the SOD activity was significantly decreased (all P<0.05), and further, the changing amplitudes of all above variables were successively decreased in the order of  model group, intraperitoneal injection group, tail vein injection group and combined injection group, and all differences had a statistical significance (all P<0.05). 
Conclusion: Bone MSC transplantation can inhibit inflammatory response, reduce oxidative stress and repair pancreatic tissue injury in SAP rats. The mechanism may be probably related to the regulation of TLR4/NF-κBp65 pathway.

Key words: Pancreatitis, Acute Necrotizing, Mesenchymal Stem Cell Transplantation, Inflammation, Toll-Like Receptor 4, Rats

CLC Number: 

  • R657.5
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