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吴雅锋, 龙翠珍, 舒远辉, 何萍, 谷俊莹, 杨蕾, 王豫萍. 大麻素受体 - 2激动剂AM1241对急性肝损伤小鼠肝组织炎性体NLRP3影响[J]. 中国公共卫生, 2019, 35(5): 571-573. DOI: 10.11847/zgggws1122242
引用本文: 吴雅锋, 龙翠珍, 舒远辉, 何萍, 谷俊莹, 杨蕾, 王豫萍. 大麻素受体 - 2激动剂AM1241对急性肝损伤小鼠肝组织炎性体NLRP3影响[J]. 中国公共卫生, 2019, 35(5): 571-573. DOI: 10.11847/zgggws1122242
Ya-feng WU, Cui-zhen LONG, Yuan-hui SHU, . Effect of cannabinoid receptor-2 agonist AM1241 on liver tissue inflammatory NLRP3 in mice with acute liver injury[J]. Chinese Journal of Public Health, 2019, 35(5): 571-573. DOI: 10.11847/zgggws1122242
Citation: Ya-feng WU, Cui-zhen LONG, Yuan-hui SHU, . Effect of cannabinoid receptor-2 agonist AM1241 on liver tissue inflammatory NLRP3 in mice with acute liver injury[J]. Chinese Journal of Public Health, 2019, 35(5): 571-573. DOI: 10.11847/zgggws1122242

大麻素受体 - 2激动剂AM1241对急性肝损伤小鼠肝组织炎性体NLRP3影响

Effect of cannabinoid receptor-2 agonist AM1241 on liver tissue inflammatory NLRP3 in mice with acute liver injury

  • 摘要:
    目的 探讨大麻素CB2受体激动剂AM1241对刀豆蛋白A(Con A)所致急性小鼠肝损伤影响及机制。
    方法 随机将40只8周龄C57BL/6J雄性小鼠分为对照组、模型组、激动剂(AM1241)3、12 mg/kg组(于造模前1 h分别腹腔注射AM1241 3、12 mg/kg),除对照组外,其余组小鼠尾静脉注射Con A 20 mg/kg复制小鼠急性肝损伤模型,对照组采用相同溶剂和方法。造模8 h后留取血清检测丙氨酸转氨酶(ALT),Western blot法分别检测炎性体3相关核苷酸结合寡聚化结构域样受体(NLRs)、凋亡相关斑点样蛋白(ASC)、半胱氨酸天冬氨酸蛋白酶 – 1(caspase-1)蛋白的表达量,利用试剂盒检测肝组织匀浆中白细胞介素1β(IL-1β)水平。
    结果 与对照组(28.5 ± 7.4)U/L比较,模型组小鼠血清ALT水平(6 132.5 ± 1 300.8)U/L明显升高(P < 0.05),肝组织中NLRP3、ASC、caspase-1蛋白表达均明显增强(P < 0.05);与模型组比较,AMl241 3、12 mg/kg组小鼠血清ALT水平分别为(2 696.5 ± 956.3)、(534.6 ± 128.6)U/L明显降低(P < 0.05),肝组织中NLRP3、ASC、caspase-1蛋白表达均有所降低(P < 0.05);与对照组比较,AMl241组小鼠肝组织中IL-1β 含量也明显降低(P < 0.05)。
    结论 CB2受体激动剂AMl241对Con A所致急性小鼠肝损伤有一定的拮抗作用,其机制可能与AM1241抑制小鼠肝组织中NLRP3、ASC、caspase-1蛋白表达,减少肝组织中炎性因子IL-1β 含量有关。

     

    Abstract:
    Objective To investigate the effect of cannabinoid receptor-2 (CB2) agonist AM1241 on nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and interleukin-1β (IL-1β) in liver tissue of mice with acute liver injury induced by concanavalin A (Con-A).
    Methods Forty 8-week-old C57BL/6J male mice were randomly divided into a control, a model, and two CB2 receptor agonist (AM1241) groups injected with AM1241 intraperitoneally at doses of 3 and 12 mg/kg one hour before the establishment of acute liver injury model with caudal vein injection of 20 mg/kg Con A in all the mice except for the control mice only with intraperitoneal injection of solvent. Eight hours after the injection of Con A, following indicators were detected for all the mice: serum alanine aminotransferase (ALT); inflammatory body 3 related nucleotide oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 in liver tissues with Western blot; and expression level of interleukin-1 beta (IL-1β) in liver homogenate with enzyme-linked immunosorbent assay (ELISA).
    Results Compared to those in the control mice, significantly increased serum ALT (6 132.5 ± 1 300.8 vs. 28.5 ± 7.4 U/L, P < 0.05), NLRP3, ASC, and caspase-1 in liver tissues (P < 0.05 for all) were detected in the model mice. In the mice administered with AMl241, significantly decreased serum ALT (2 696.5 ± 956.3 and 534.6 ± 128.6 U/L, both P < 0.05), NLRP3, ASC and caspase-1 protein in liver tissues (all P < 0.05) were detected in comparison with those in the model mice. Significantly decreased IL-1β in liver homogenate was also detected in the mice with AMl241 treatment compared to that in the control mice (P < 0.05).
    Conclusion CB2 receptor agonist AMl241 may have protective effects on Con A-induced acute liver injury in mice and the effects may be related to inhibitions of NLRP3, ASC, caspase-1, and IL-1β expression in liver tissue of mice.

     

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