中文摘要：

目的：建立半胱氨酰白三烯受体2（CysLT2受体）拮抗剂筛选的细胞模型及方法,初筛系列合成化合物。方法：选用高表达CysLT2受体的大鼠C6胶质瘤细胞,激动剂LTD4攻击后检测细胞内钙浓度变化,作为CysLT2受体拮抗剂的筛选方法,初步筛选有拮抗剂活性的化合物。采用CysLT1/CysLT2受体非选择性拮抗剂Bay u9773和CysLT2受体选择性拮抗剂AP-100984作为参照。结果：RT-PCR鉴定表明C6细胞高表达CysLT2受体。LTD41μmol/L能显著升高C6细胞内钙,其作用约为阳性对照ATP的37.5%。CysLT2受体拮抗剂抑制LTD4诱导的C6细胞内钙升高,CysLT1受体选择性拮抗剂无抑制作用。化合物中DXW-1、2、13、23、29、30能抑制LTD4诱导的细胞内钙升高。结论：LTD4诱导的C6细胞的钙信号变化可作为CysLT2受体拮抗剂的筛选方法;化合物DXW-1、2、13、23、29、30具有CysLT2受体拮抗活性。

英文摘要：

Objective： To establish a method for screening cysteinyl leukotriene receptor 2 （CysLT2） antagonists and to preliminarily screen a series of synthetic compounds. Methods： Rat glioma cell line （C6 ceils） highly expressing CysLT2 receptor was used. Intracetlular calcium concentration was measured after stimulation with the agonist LTD4,which was used to screen compounds with antagonist activity for CysLT2 receptor. Bay u9773,a CysLT1/CysLT2 receptor non selective antagonist, and AP 100984, a CysLT2 receptor antagonist, were used as control. Results ： PT-PCR showed a higher expression of CysLT2 receptor in C6 cells. LTD4 at 1μmol/L significantly increased intracellular calcium in C6 cells; the maximal effect was about 37.5% of ATP,a positive stimulus. LTD4 induced increase of intracellular calcium was blocked by CysLT2 receptor antagonists,but not by CysLT1 receptor antagonists. Among the synthetic compounds, Dxw-1,2,13,23,29 and 30 inhibited LTD4 induced increase of intracellular calcium. Conclusions ： LTD4-induced change in intracellular calcium in C6 cells can be used as a screening method for CysLT2 receptor antagonists. The compounds,Dxw 1,2, 13, 23, 29 and 30, possess antagonist activity for CysLT2 receptor.