肿瘤免疫治疗已成为继肿瘤手术、放疗和化疗同等重要的第四种肿瘤治疗模式。基于对肿瘤生物学和免疫学原则的不断深入研究，提高抗肿瘤细胞免疫功能、消除肿瘤细胞对免疫细胞抑制性因素，已发展为免疫治疗的重要策略。细胞程序性死亡－1（ Programmed Death 1，PD－1）是近年来发现的负性刺激分子之一，为Ⅰ型跨膜糖蛋白，分子大小为55 kD，属于CD28型家族，作为抑制分子表达于活化的T细胞和B细胞表面。肿瘤细胞表面表达和分泌细胞程序性死亡配体－1（ Programmed Death 1 Ligand， PD－L1），PD－L1与肿瘤浸润淋巴细胞表面的PD－1分子结合后，会抑制T、B淋巴细胞的活性，是肿瘤细胞逃避机体免疫的主要原因之一［1］。因此在肿瘤免疫治疗中，基于PD－1为靶点的免疫治疗药物成为研发的热点。现就PD－1／PD－L1通路在免疫调节中的作用及其在免疫治疗方面的研究进展进行综述。
Objective To develop a HPLC-MS/MS method for the determination of aconitine and study the in vitro metabolic stability of aconitine in dog tssue homogenates.Methods The chromatographie separation was performed on a Cg column.The mo-bile phase consisted of acetonitile and water with 0.2%formic acid and 5 mmol/L ammonium acetate.A triple quadrupole tandem mass spectrometer equipped with an electrospray ionization interface source was used for the quantitative determination in the positive selective reaction monitor mode.Aconitine was incubated with dog tissue homogenates and samples were withdrawn at different time points and precipitated by acetonitrile with internal standards citalopram.Results Aconitine showed good linear relationship over the range from5 to 500 ng/ml.The recoveries of aconitine were between 85.73%and 92.12%at three QC concentration levels.The in-tra-and inter-day precisions were 5.32%-8.95%and 5.45%-8.86%,respectively.After incubation,about 20%of aconitine were cleared in the liver and small intestine,and ln were 460.6 and 521.3 min,respectively.But none was metabolized in the stom-ach and kidney.Conclusion These results demonstrated that aconitine was mainly metabolized in the liver and small intestine at a slow rate.
YANG Cui-pingLIAO ShaZHANG Tian-hongLI Jing-laiWANG Xiao yingRUAN Jjin-xiuZHANG Zhen-qing
