腹腔注射川芎嗪对哮喘大鼠Th_1/Th_2细胞因子的影响及机制

Effects and action mechanism of intraperitoneal injection of ligustrazine on Th_1/Th_2 cytokines in a rat asthma model

目的探讨腹腔注射川芎嗪对哮喘大鼠模型Th1/Th2细胞因子表达的影响及其机制。方法40只SD大鼠随机分为正常对照组(Con组),哮喘组(Ast组),哮喘生理盐水对照组(Ast-C组),川芎嗪组(Lig组),地塞米松组(Dex组),每组8只。ELISA检测支气管肺泡灌洗液(BALF)中IL-4和IFN-γ的浓度并进行嗜酸性粒细胞(EOS)计数,同时用免疫组化法检测肺组织GATA-3和T-bet蛋白的表达。结果①Ast组及Ast-C组大鼠BALF中EOS均高于Con组,而Lig组和Dex组均低于Ast组及Ast-C组(P<0.05)。②与Con组相比,Ast组及Ast-C组BALF中IL-4和肺组织GATA-3水平均明显升高,IFN-γ和T-bet水平明显减低(P<0.05)。③与Ast组及Ast-C组相比,Lig组BALF中IL-4和肺组织GATA-3水平均明显降低(P<0.05),IFN-γ和T-bet水平明显升高(P<0.05),而Dex组IL-4、IFN-γ、GATA-3和T-bet水平则均降低(P<0.05),IL-4和GATA-3分别比IFN-γ和T-bet减低更明显。结论川芎嗪可通过使哮喘肺组织GATA-3下调、T-bet上调进而调节Th1/Th2细胞因子比例,从而扭转哮喘时的Th2细胞优势,改善相应炎性症状。

[ Objective ] To investigate the effects of intraperitoneal injection of ligustrazine on Th1/Th2 cytokines in a rat asthma model and the underlying mechanism. [ Methods ] Forty male SD rats were randomly divided into 5 groups ： normal control group, asthmatic model group, asthmatic control group, ligustrazine group and dexamethasone （Dex） group. The concentrations of IL-4 and IFN-γ, in bronchoalveolar lavage fluid （BALF） were measured by enzyme-linked immunosobent assay （ ELISA）, meanwhile eosinophil （EOS） counts were performed. The protein expressions of GATA-5 and T-bet in pulmonary tissue were detected with immunohistochemical assay. [ Results ] In asthmatic and asthmatic control group, the EOS% , evel of IL-4 in BALF and the expression of GATA-5 of lung were higher than those in normal control group, while the levels of IFN-γ, and T-bet were significantly decreased （ P 〈 0.05 ）. Compared with asthmatic group and asthmatic control group, the EOS%, level of IL-4 in BALF and the expression of GATA-3 of hmg in ligustrazine group were both lower（ P 〈 0.05）, and the levels of IFN-γ, and T-bet were both higher （ P 〈 0.05） , while all of EOS% , IL-4, IFN-γ,, GA- TA-3 and T-bet decreased in Dex group（ P 〈 0.05 ）, but the decreasing degrees of IL-4, GATA-3 were greater than that of IFN-γ, T-bet, respectively. [ Conclusion ] Ligustrazine treatment inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in reversing the Th2 cytokine patterns in asthma.