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Effects of allogeneic bone marrow mesenchymal stem cells on the polarization of peritoneal macrophages in rats with acute necrotizing pancreatitis

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Author:
No author available
Journal Title:
Chinese Journal of Pancreatology
Issue:
2
DOI:
10.3760/cma.j.cn115667-20190918-00081
Key Word:
胰腺炎,急性坏死性;巨噬细胞;间充质干细胞;极化;大鼠;Pancreatitis, acute necrotizing;Macrophages;Mesenchymal stem cells;Polarization;Rat

Abstract: Objective:To study the effects of bone marrow mesenchymal stem cells (BMSCs) on the inflammatory response and polarization of peritoneal macrophages in rats with acute necrotizing pancreatitis (ANP).Methods:Thirty Sprague Dawley male rats were divided into control group, ANP group, low-dose (0.5×10 6 cells), medium-dose(1×10 6 cells)and high-dose (2×10 6 cells)BMSCs treatment groups. ANP model was established via the retrograde injection of 1ml/kg 5% sodium taurocholate hydrate into pancreaticobiliary duct. BMSCs were injected via caudal vein 1 h after molding. Tissues of the rat pancreas were taken for pathological examination, and iNOS and ARG1 positive macrophages were detected by immunohistochemistry. The level of amylase, TNF-α, IL-1β and MPO were measured in peripheral blood. Abdominal macrophages were obtained by intraperitoneal perfusion, and TNF-α and iNOS mRNA expression of macrophages were detected by real-time fluorescence quantitative PCR; and the dynamic changes of M1(F4/80 + , CCR2 + ) and M2 (F4/80 + , CD 163+ ) macrophages were detected by flow cytometry. Results:The pathological injury of pancreatic tissue in the three treatment groups was obviously less serious than that of ANP group. In ANP group, more iNOS and ARG1 positive macrophages were present in rat pancreatic tissue, while none or only few iNOS and ARG1 positive macrophages were observed in control group and treatment group. The therapeutic effects of medium dose (1×10 6)BMSCs treatment group was significantly better than those of the other two treatment groups, with statistically significant differences(all P<0.05). Compared with ANP group, TNF-α[ (99.5±11.8)ng/L vs (185.5±27.5)ng/L ], IL-1β[ (24.1±3.7)ng/L vs (128.5±66.1)ng/L ], MPO [ (643.8±98.4)ng/L vs (2131.9±261.4)ng/L ], TNF-α (2.16±0.98 vs 6.53±3.45) and iNOS (2.32±1.88 vs 7.37±2.98) mRNA expression in peritoneal macrophages, and the ratio of M1/M2 (1.53±0.10 vs 2.02±0.31)were all greatly decreased, and the differences were all statistically significant (all P<0.05), except for blood amylase. All the above indexes in ANP group and the three treatment groups were all significantly higher than those in the control group, with statistically significant differences (all P<0.05). Conclusions:Intravenous infusion of allogeneic BMSCs can inhibit the M1 type polarization of peritoneal macrophages, reduce the M1/M2 ratio of peritoneal macrophages, and alleviate the inflammatory response in ANP rats.

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