P2X7R抑制剂BBG对小鼠异基因造血干细胞移植后aGVHD的抑制作用研究

发布时间：2019-02-15 01:17

【摘要】：目的:探讨P2X7R抑制剂酸性亮蓝G(brilliant blue G,BBG)对小鼠异基因造血干细胞移植(allo-HSCT)后急性移植物抗宿主病(aGVHD)发生的影响。方法:建立小鼠allo-HSCT后并发aGVHD模型,通过不同剂量P2X7R抑制剂BBG(50和75 mg/kg)给药处理,观察受鼠生存情况、体重变化,检测肝脏病理变化及肝功能改变,检测肝脏P2X7R、NLRP3、Caspase-1、IL-1β、IL-18 mRNA及相关蛋白表达的变化。结果:成功建立小鼠allo-HSCT后并发aGVHD模型。腹腔注射BBG可减轻受鼠弓背、竖毛、皮肤剥脱、体重下降等aGVHD的临床表现;减轻受鼠肝脏水肿、出血、坏死等病理改变,改善受鼠的肝功能;降低受鼠肝脏P2X7R、IL-1β蛋白的表达;降低受鼠肝脏P2X7R、NLRP3、Caspase-1、IL-1β、IL-18因子mRNA表达;且aGVHD+75 mg/kg BBG组受鼠各项指标变化最为显著。结论:BBG可减轻allo-HSCT后aGVHD引起的肝脏炎性损伤,减少炎性因子分泌,且75 mg/kg BBG组的保护作用优于50 mg/kg BBG组。
[Abstract]:Aim: to investigate the effect of acid brilliant blue G (brilliant blue (G (brilliant blue), a P2X7R inhibitor, on the occurrence of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mice. Methods: aGVHD model was established after allo-HSCT in mice. The survival status, body weight, liver pathological changes and liver function of recipient mice were observed by different dosage of P2X7R inhibitor BBG (50 and 75 mg/kg), and P2X7R of liver were detected. Expression of NLRP3,Caspase-1,IL-1 尾, IL-18 mRNA and related proteins. Results: aGVHD model was successfully established after allo-HSCT in mice. Intraperitoneal injection of BBG could alleviate the clinical manifestations of aGVHD, such as bow-back, vertical hair, skin exfoliation, weight loss, and other pathological changes, such as edema, hemorrhage and necrosis of liver, and improve the liver function of recipient rats. The expression of P2X7Rnl 尾 protein and the expression of IL-1 尾, IL-18 factor of P2X7RNLP3Caspase-1 mRNA in recipient liver were decreased, and the changes of various indexes in aGVHD 75 mg/kg BBG group were most significant. Conclusion: BBG can attenuate the hepatic inflammatory injury induced by aGVHD and reduce the secretion of inflammatory factors after allo-HSCT, and the protective effect of 75 mg/kg BBG group is better than that of 50 mg/kg BBG group.
【作者单位】：南京医科大学附属淮安第一医院肿瘤科;徐州医学院附属医院血液科;
【基金】：国家自然科学基金面上项目(81270637)
【分类号】：R457.7

【相似文献】