纳布啡在尿毒症瘙痒小鼠模型中的作用以及对IL-10和IL-31的影响  

Effect of Nalbuphineon uremic pruritus mouse model and IL-10 and IL-31

作　　者：李慧利[1] 高巍巍 戴佳佳 王奕童 郑德利[1] 杜亮 曹金骥 Li Huili;Gao Weiwei;Dai Jiajia;Wang Yitong;Zheng Deli;Du Liang;Cao Jinji(Department of Anesthesiology,the First Hospital of Hebei Medical University,Shijiazhuang Hebei 050000,China;Hengshui Hospital of Traditional Chinese Medicine,Hengshui Hebei 053000,China)

机构地区：[1]河北医科大学第一医院麻醉科,河北石家庄050000 [2]衡水市中医医院,河北衡水053000

出　　处：《遵义医科大学学报》2023年第2期140-144,151,共6页Journal of Zunyi Medical University

基　　金：河北省医学科学研究项目(NO:20190417)。

摘　　要：目的探讨纳布啡在尿毒症瘙痒小鼠模型中的作用以及对IL-10和IL-31的影响。方法将C57BL/6J小鼠分为3组,分别为对照组、模型组和纳布啡组,每组20只。纳布啡组静脉注射纳布啡0.6 mg/kg,对照组和模型组注射同体积0.9%氯化钠溶液。进行小鼠瘙痒行为学观察;HE染色观察小鼠皮肤病理改变;ELISA法检测血清中IL-10和IL-31;Western blot实验检测组织中IL-10、IL-31、FoxP3、CD80、CD163和iNOS的表达;Real-time PCR检测免疫细胞标志物。结果1~21 d,模型组和纳布啡组小鼠搔抓次数明显高于对照组(P<0.05),第14天和第21天,纳布啡组小鼠搔抓次数显著低于模型组(P<0.05);对照组皮肤组织病例尚未出现炎症细胞因子浸润和皮肤的改变。模型组皮肤组织可见大量炎症细胞,主要为嗜酸性粒细胞、淋巴细胞;与模型组对比,纳布啡组炎症细胞的浸润明显减少;与对照组相比,模型组小鼠血清中和组织中IL-10的表达以及蛋白表达明显降低(P<0.05);与模型组相比,纳布啡组小鼠血清中和组织中IL-10的表达以及蛋白表达显著升高(P<0.05);与对照组相比,模型组小鼠血清中和组织中IL-31的表达以及蛋白表达明显升高(P<0.05);与模型组相比,纳布啡组小鼠血清中和组织中IL-31的表达以及蛋白表达显著降低(P<0.05);对照组、模型组、纳布啡组中FoxP3、CD80和CD163蛋白和mRNA表达对比无显著性差异(P>0.05),与对照组相比,模型组小鼠血清中和组织中iNOS蛋白和mRNA的表达升高(P<0.05);与模型组相比,纳布啡组小鼠血清中和组织中iNOS蛋白和mRNA表达显低(P<0.05)。结论纳布啡对小鼠尿毒症瘙痒有明显的抑制作用,能够增加抗炎IL-10水平,降低IL-31,也能够降低少部分免疫细胞标志物的表达。Objective To investigate the effect of nalbuphine on uremic pruritus mouse model and potential mechanism related to IL-10 and IL-31.Methods C57BL/6J mice were divided into three groups:control group,model group and naborphine group,with 20 mice in each group.The mice in naborphine group were injected with 0.6 mg/kg naborphine intravenously,and the control and model group with 0.9%sodium chloride solution of the same volume.The pruritus behavior of mice was observed.HE staining was used to observe the pathological changes of mouse skin.IL-10 and IL-31 in serum were detected by ELISA.Western blot was used to detect the expressions of IL-10,IL-31,FoxP3,CD80,CD163 and iNOS in tissues.Macrophage markers were detected by real time PCR.Results From day 1 to day 21,the number of scratching in the model group and naborphine group was significantly higher than that in the control group(P<0.05),and the number of scratching in the naborphine group was significantly lower than that in the model group(P<0.05).There was no inflammatory cytokine infiltration and skin changes in the control group.In the model group,there were a large number of inflammatory cells,mainly eosinophils and lymphocytes;The number of infiltrating cells in naborphine group was significantly lower than that in naborphine group.Compared with the control group,the expression of IL-10 and protein in serum and tissues of the model group decreased significantly(P<0.05).Compared with the model group,the expression of IL-10 and protein in serum and tissues in naborphine group were significantly higher(P<0.05).Compared with the control group,the expression of IL-31 and protein in serum and tissues of the model group were significantly higher(P<0.05).Compared with the model group,the expression of IL-31 and protein in serum and tissues in naborphine group were significantly lower(P<0.05).There was no significant difference in the expression of Foxp3,CD80 and CD163 protein and mRNA among the control group,model group and naborphine group(P>0.05).Compared with the c

关 键 词：尿毒症瘙痒 纳布啡 阿片受体 IL-10 IL-31 

分 类 号：R969.4[医药卫生—药理学]