血清药理学方法观察氯吡格雷对人胃黏膜上皮细胞GES-1的影响  

Study on Serum Pharmacological Effect of Clopidogrel on Human Gastric Mucosal Epithelial Cells GES-1

作　　者：吴海露[1] 张振玉[1] 高欣[1] 姜宗丹[1] 胡可伟[1] 何帮顺[2] 

机构地区：[1]南京医科大学附属南京第一医院消化科,210006 [2]南京医科大学附属南京第一医院中心实验室,210006

出　　处：《胃肠病学》2012年第6期334-337,共4页Chinese Journal of Gastroenterology

摘　　要：背景:氯吡格雷可引起胃肠道不良反心尤其是消化道出血,前期研究已证实氯吡格雷原药对人胃黏膜上皮细胞GES-1增殖具有抑制作用。然而,氯吡格雷经肝脏代谢后对胃黏膜上皮细胞是否具有损伤作用目前尚无报道。目的:通过血清药理学办法研究氯吡格雷含药血清体外对人胃黏膜上皮细胞侏GES-1的影响,以探讨氯吡格雷对人胃黏膜的损伤作用。方法:分离1例服用氯吡格雷(75 mg/d)一年而导致消化道出血患者的血清,并配置成浓度分别为5%、10%、15%、20%的含药血清,同时取该患者停用氯吡格雷10 d后的血清作为对照。与GES-1细胞共同培养24 h后,以倒置相差显微镜观察细胞形念学变化,MTT法和流式细胞术分别检测细胞增殖、凋亡情况。结果:与对照组相比,不同浓度的含药血清可使GES-1细胞变圆、核浓缩,对GES-1细胞均有抑制增殖、促进凋亡的效应,并呈一定的浓度依赖性。结论:氯吡格雷经肝脏代谢后的产物对人胃黏膜上皮细胞具有损伤作用。Clopidogrel can induce gastrointestinal side effects, especially gastrointestinal bleeding. Previous studies have demonstrated that clopidogrel has an inhibitory effect on the proliferation of human gastric mucosal epithelial cells GES-1. However, whether clopidogrel＇ s hepatic metabolites having damaging effects on gastric mucosal epithelial cells has not been reported yet. Aims： To investigate the effect of clopidogrel＇ s hepatic metabolites on proliferation of human gastric mucosa epithelial cells GES-1 in vitro by serum pharmacology assay, and assess the injury of human gastric mucosa caused by clopidogrel. Methods： Serum was separated from a patient with gastrointestinal bleeding caused by taking clopidogrel 75 mg/d for one year, and 5% , 10%, 15% , 20% concentrations of clopidogrel-contained serum were prepared. Serum separated from the same patient 10 days after stopping the using of clopidogrel was served as control. After co-culturing with GES-1 cells for 24 hours, morphologic changes were observed by inverted phase contrast microscope, MTT and flow cytometry were used to detect proliferation and apoptosis of GES-1 cells, respectively. Results： Compared with the control group, cell rounding and nuclear condensation were seen in different concentrations of clopidogrel-contained serum groups, and clopidogrel-contained serum inhibited the proliferation of GES-1 cells and induced cell apoptosis in a concentration-dependent manner. Conclusions： The hepatic metabolites of clopidogrel could damage human gastric mucosal epithelial cells.

关 键 词：氯吡格雷 人胃黏膜上皮细胞 血清 药理学 细胞增殖 细胞凋亡 

分 类 号：R96[医药卫生—药理学]