苦参碱通过下调SOCS3表达抑制支气管哮喘大鼠炎性反应并调节Th1/Th2平衡

Matrine suppresses inflammation and corrects Th1/Th2 imbalance in asthmatic rats via down-regulating SOCS3

目的探讨苦参碱减轻支气管哮喘大鼠炎性反应、纠正Th1/Th2失衡的作用,以及SOCS3在此过程中的表达变化。方法将大鼠分为对照组、模型组(卵清蛋白致敏法构建大鼠急性哮喘模型)和药物干预A组及B组(建模成功后,分别接受60和120 mg/kg的苦参碱治疗)。计算支气管肺泡灌洗液(BALF)中的嗜酸粒细胞(EOS)绝对值、EOS百分比及肺组织中的杯状细胞百分比和炎性细胞浸润积分。酶联免疫法分析BALF中的IFN-γ和IL-4水平,并计算IFN-γ/IL-4。荧光实时定量PCR(qRT-PCR)和Western blot分析肺组织中细胞因子传导抑制因子3(SOCS3)mRNA与蛋白的表达。结果模型组大鼠BALF中EOS计数、EOS百分比、杯状细胞百分比、炎性细胞浸润评分和IL-4水平,肺组织中的SOCS3 mRNA及蛋白表达均较对照组显著增高(P<0.05)。而BALF中IFN-γ水平显著降低(P<0.05)。低剂量和高剂量苦参碱分别显著缓解模型组的上述变化(P<0.05)。结论苦参碱可以抑制支气管哮喘大鼠炎性反应、纠正Th1/Th2的失衡,该过程中存在SOCS3的表达变化。苦参碱可能通过降低SOCS3表达调节Th1/Th2的平衡。

Objective To investigate the inhibitory effect of matrine on inflammation by regulating Th1/Th2 balance in asthmatic rats and the underlying mechanism related to SOCS3. Methods Ovalbumin-sensitized rats were established as asthma model,Animals randomly divided into four groups,as follows： control（ without any treatment）,model group,treatment group A（ low-dose matrine treated asthma rats） and treatment group B（ high-dose matrine treated asthma rats）. The eosinophil counting,goblet cells percentage,inflammatory cell infiltration in rat lung were analyzed and scored by morphological examination. IL-4 and IFN-γ level in BALF were determined by ELISA and IFN-γ/IL-4 ratio was further calculated. Furthermore,the expression of SOCS3 in mRNA and protein level were detected by qRT-PCR and Western blot,respectively. Results Eosinophil count and percentage,goblet cell percentage and inflammatory cell infiltration score were significantly lower than that intreatment group A and B as compare to model group（ P〈 0. 05）. The group A exhibited a lower IFN-γ level and a higher IL-4 level（ P 〈0. 05）. IFN-γ level in treatment group A and B were higher while IL-4 level were lower as compare to model group. Meanwhile,SOCS3 mRNA level in rat lung tissue was elevated in model group. Matrine treatment decreased SOCS3 expression in group A and B. Similar trend was found in SOCS3 protein level.Conclusions Matrine may exhibit antiinflammatory effect by inhibiting SOCS3 expression and correcting Th1 /Th2 balance in asthmatic rats.