白藜芦醇通过线粒体调控血吸虫感染小鼠M1/M2极化

目的探讨白藜芦醇对血吸虫病巨噬细胞极化的作用及机制。方法45只血吸虫感染小鼠3周后,随机分3组,A组感染组,B组白藜芦醇治疗组,C组吡喹酮治疗组,另取15只小鼠为健康对照D组。感染第9周,流式细胞术检测肝脏M1、M2,ATP试剂盒检测肝脏巨噬细胞ATP,实时定量PCR检测M1和M2相关因子、mtDNA。采用虫卵可溶性抗原(SEA)刺激RAW264.7,再给予白藜芦醇处理,检测M1、M2比例,细胞上清中M1和M2相关因子,PGC-1α,mtDNA和ATP。结果B组M1比例高于A组(P<0.01),M2比例低于A组(P<0.05),肝脏巨噬细胞M2相关因子、PGC-1α、mtDNA、ATP、基础耗氧率均低于A组(P<0.05),M1相关因子高于A组(P<0.05)。白藜芦醇使RAW264.7往M1分化增多(P<0.01),往M2分化减少(P<0.01),M2相关因子降低(P<0.05),mtDNA、PGC-1α、ATP、基础耗氧率降低(P<0.05),M1相关因子增高(P<0.05)。结论白藜芦醇通过抑制巨噬细胞线粒体数量和功能促进其往M1分化,抑制其往M2分化。

Resveratrol regulates M1/M2 polarization of mice infected with schistosoma japonicum through mitochondria

Aim To investigate the effect of resveratrol on the polarization of macrophages and its correlation with mitochondrion.Methods Fifty-five mice infected with Schistosoma japonicum for three weeks were randomly divided into three groups:infection group(A),resveratrol group(B)and praziquantel group(C).Fifteen normal mice were taken as normal control group(D).On 9th week of infection,M1 and M2 were measured by flow cytometry(FCM),the mRNA level of M1 and M2 related cytokines,PGC-1αand mtDNA level were detected by RT-PCR,and the ATP production was detected by ATP kit.RAW264.7 cells were stimulated by PBS and SEA respectively.Resveratrol and praziquantel were added after stimulation.The percents of M1 and M2 were detected by FCM.PGC-1αand mtDNA level were detected by RT-PCR.The level of M1 and M2 related cytokines were measured by ELISA.ATP was detected by ATP assay kit.Results Compared to group A,the proportion of M1 in group B increased(P<0.05),and the proportion of M2 decreased(P<0.01).The levels of M2 related cytokines,PGC-1α,mtDNA,ATP,basal OCR(oxygen comsumpition rate)in liver macrophages in group B were lower than those in group A(P<0.05).The levels of M1 related cytokines in group B were evidently higher than those in group A(P<0.05).RAW264.7 cells were polarized into M1(P<0.05),but not M2(P<0.05)under resveratrol treatment.Moreover,RAW264.7 cells with resveratrol treatment produced less M2 related cytokines(P<0.05),mtDNA,PGC-1α,ATP and basal OCR(P<0.05),and more related cytokines(P<0.05).Conclusion Resveratrol shifts macrophage polarization from M2 towards M1 by inhibiting the synthesis and ATP production of mitochondria.