Xiong Liang, Fang Zheng-Yu, Tao Xiao-Nan, Bai Ming, Feng Gang
Key Lab of Pulmonary Diseases of Ministry of Health, Department of Respiratory Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Am J Chin Med. 2007;35(6):1011-20. doi: 10.1142/S0192415X07005478.
Ligustrazine is an alkaloid isolated from the rhizome of Chuanxiong (Ligusticum chuanxiong Hort), which is known to possess antioxidant, anti-inflammatory, anti-fibrosis and immunomodulative effects. It is used clinically to treat asthma as an assistant therapy of glucocorticoid. The purpose of this study was to explore the effects of intraperitoneal ligustrazine on Th1/Th2 cytokines in a rat asthma model and the underlying mechanism. SD rats were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. Within 24 hours after the last ovalbumin challenge, changes in airway histology were observed. The concentrations of IL-4 and IFN-gamma in bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). The protein expressions of GATA-3 and T-bet in lung were measured by Western blot. The results showed that an increase of Th2 cytokine and an inhibition of Th1 cytokine were accompanied by an increased expression of GATA-3 protein and a decreased expression of T-bet protein in rat asthmatic airways compared to those in normal control group. Intraperitoneal ligustrazine administration could significantly lower the level of IL-4 in BALF and the expression of GATA-3 protein in lung and also increase the level of IFN-gamma and T-bet in asthmatic rats, resulting in a decreased percentage of eosinophils (EOS) in BALF and ameliorated airway inflammatory cell infiltration. In conclusion, ligustrazine 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.
川芎嗪是从川芎（Ligusticum chuanxiong Hort）根茎中分离出的一种生物碱，已知其具有抗氧化、抗炎、抗纤维化和免疫调节作用。临床上它作为糖皮质激素的辅助疗法用于治疗哮喘。本研究的目的是探讨腹腔注射川芎嗪对大鼠哮喘模型中Th1/Th2细胞因子的影响及其潜在机制。将SD大鼠用卵清蛋白（OVA）致敏并激发以建立哮喘模型。在最后一次卵清蛋白激发后24小时内，观察气道组织学变化。采用酶联免疫吸附测定（ELISA）法检测支气管肺泡灌洗液（BALF）中IL-4和IFN-γ的浓度。采用蛋白质免疫印迹法检测肺组织中GATA-3和T-bet的蛋白表达。结果显示，与正常对照组相比，大鼠哮喘气道中Th2细胞因子增加、Th1细胞因子受到抑制，同时伴有GATA-3蛋白表达增加和T-bet蛋白表达减少。腹腔注射川芎嗪可显著降低哮喘大鼠BALF中IL-4水平和肺组织中GATA-3蛋白表达，还可提高哮喘大鼠中IFN-γ和T-bet水平，导致BALF中嗜酸性粒细胞（EOS）百分比降低，气道炎性细胞浸润减轻。总之，川芎嗪通过调节关键主开关GATA-3和T-bet来抑制OVA诱导的气道炎症，从而逆转哮喘中Th2细胞因子模式。
