激活CB_(2)受体对MPP+诱导BV2小胶质细胞iNOS和Arg-1表达的影响

EFFECT OF ACTIVATION OF CB_(2)RECEPTOR ON INOS AND ARG-1 EXPRESSION IN MPP+-INDUCED BV2 MICROGLIA

目的探讨激活大麻素Ⅱ型受体(CB_(2)受体)对1-甲基-4-苯基吡啶离子(MPP+)处理的BV2小胶质细胞M1/M2表型转化的影响。方法培养BV2小胶质细胞,将其分为对照组、MPP+组、JWH133(CB_(2)受体激动剂)+MPP+组、AM630(CB_(2)受体抑制剂)+MPP+组、JWH133+AM630+MPP+组。应用免疫印迹法检测各组诱导型一氧化氮合酶(iNOS)和精氨酸酶-1(Arg-1)蛋白的表达。结果与对照组相比,MPP+组BV2小胶质细胞iNOS蛋白表达明显上升(F=9.825,q=6.346,P<0.01);JWH133预处理抑制MPP+诱导的iNOS蛋白的上调(q=5.714,P<0.01),此抑制作用可被AM630逆转(q=4.154,P<0.05)。与MPP+组相比,JWH133预处理显著上调Arg-1蛋白表达水平(F=5.800,q=5.520,P<0.01),此作用可被AM630所阻断(q=4.155,P<0.05)。结论激活CB 2受体可抑制MPP+处理的BV2小胶质细胞M1极化,并且促进BV2小胶质细胞从M1型转化为M2型。

Objective To investigate the effect of activation of cannabinoid 2 receptor(CB_(2)receptor)on the M1/M2 phenotypic transition in BV2 microglia treated with 1-methyl-4-phenylpyridinium(MPP+).Methods BV2 microglia were cultured and divided into control group,MPP+group,JWH133(CB 2 receptor agonist)+MPP+group,AM630(CB 2 receptor antago-nist)+MPP+group,and JWH133+AM630+MPP+group.Western blot was applied to determine the expression of inducible nitric oxide synthase(iNOS)and agrinase-1(Arg-1)proteins in each group.Results Compared with the control group,the MPP+group had significantly increased iNOS protein expression in BV2 microglia(F=9.825,q=6.346,P<0.01);JWH133 pretreatment inhibited MPP+-induced upregulation of iNOS protein(q=5.714,P<0.01),and the inhibitory effect of JWH133 could be reversed by AM630(q=4.154,P<0.05).Compared with the MPP+group,JWH133 pretreatment significantly upregulated the expression level of Arg-1 protein(F=5.800,q=5.520,P<0.01),and the upregulation effect could be blocked by AM630(q=4.155,P<0.05).Conclusion Activation of CB_(2)receptor inhibits M1 polarization in MPP+-treated BV2 microglia and promotes the transformation of BV2 microglia from M1 phenotype to M2 phenotype.