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嘌呤能2X7受体-核苷酸结合寡聚化结构域样受体3信号通路活化在慢性胰腺炎纤维化中的作用 被引量:3

Role of Purinergic 2X7 Receptor-Nucleotide-binding Oligomerization Domain Receptor 3 Signal Pathway Activation in the Fibrosis of Chronic Pancreatitis
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摘要 目的:探讨嘌呤能2X7受体(P2X7R)-核苷酸结合寡聚化结构域样受体3(NLRP3)炎性体信号通路在小鼠慢性胰腺炎模型胰腺纤维化进程中的作用。方法:通过反复腹腔注射雨蛙素造成小鼠慢性胰腺炎模型,分别用P2X7R拮抗剂氧化三磷酸腺苷(Ox ATP)和亮蓝G(BBG)进行干预,处死后观察胰腺组织病理学变化,并用Western Blot及RT-PCR法对P2X7R、NLRP3和半胱天冬酶1(caspase-1)的含量进行检测,比较各组的变化。结果:正常对照组的P2X7R、NLRP3和caspase-1的蛋白表达水平分别为0.85±0.18,、0.93±0.16和1.02±0.06,模型组分别是1.55±0.22、2.00±0.35和2.23±0.56,二组比较,均有差异。OxATP组分别为1.02±0.26、1.01±0.09和0.95±0.04,BBG组分别为0.97±0.17、0.96±0.14和2.07±0.33,与模型组相比,无论是OxATP组还是BBG组,P2X7R、NLRP3和caspase-1在胰腺组织中的表达均显著降低(P<0.05)。病理结果显示,模型组出现了明显的胰腺纤维化,而OxATP组和BBG组的慢性胰腺炎和纤维化指标明显改善。结论:OxATP和BBG能够降低慢性胰腺炎模型的慢性炎症和纤维化程度,其机制与抑制P2X7R-NLRP3-caspase1信号通路的活化有关。 Objective To investigate the role of purinergic 2X7 receptor(P2X7R)-NLRP3 signaling path- way in the process of pancreatic fibrosis in a mouse model of chronic pancreatitis. Methods Chronic pancre- atitis model was induced by repeated intraperitoneal injections of caerulein. The P2X7R antagonists OxATP and (brilliant blue G, BBG) were given to respective groups. Then, all mice were sacrificed and the histopathological changes of the pancreas,especially the fibrotic degrees,were observed. Caspase-1, NLRP3 and P2X7R were de- tected by Western Blot and RT-PCR and compared among the groups. Results The protein expression levels of P2X7R, NLRP3 and caspasel in the normal control group were 0.85±0.18, 0.93±0.16 and 1.02±0.06, while 1.55±0.22, 2.00±0.35 and 2.23±0.56 in the model group. Significant differences were found in these parameters as compared to control values. The respective values for these parameters were 1.02±0.26,1.01±0.09 and 0.95± 0.04 in the OxATP group and 0.97±0.17, 0.96±0.14 and 2.07±0.33 in the BBG group. In both OxATP and BBG group, the expression of P2X7R, NLRP3 and caspasel in pancreatic tissue were significantly decreased, com- pared with the model group (P 〈 0.05). Pathological results showed that the pancreatic fibrosis was obvious in the model group, while the chronic inflammation and fibrosis indexes of the OxATP and the BBG groups were significantly improved. Conclusion P2X7R antagonists OxATP and BBG significantly decreased pancreatic chronic inflammation and fibrosis in a mouse model of chronic pancreatitis and the mechanism may be associat- ed with an inhibition of the P2X7R- NLRP3-Caspasel signaling pathway.
出处 《中国中西医结合外科杂志》 CAS 2017年第3期278-282,共5页 Chinese Journal of Surgery of Integrated Traditional and Western Medicine
基金 天津市卫生计生委科技基金项目(2014KY39)
关键词 慢性胰腺炎 胰腺纤维化 嘌呤能2X7受体 核苷酸结合寡聚化结构域样受体3炎性体 Chronic pancreatitis pancreatic fibrosis purinergic 2X7 receptor NLRP5 infiammasome
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