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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。
BACKGROUND: Clopidogrel can cause gastrointestinal adverse reactions, especially gastrointestinal bleeding. Previous studies have shown that clopidogrel can inhibit the proliferation of human gastric mucosal epithelial cells GES-1. However, clopidogrel metabolized by the liver on the gastric mucosal epithelial cells have no role in injury has not been reported. OBJECTIVE: To study the effect of clopidogrel-containing serum on GES-1 in human gastric mucosal epithelial cells by serum pharmacology to explore the effect of clopidogrel on human gastric mucosa. Methods: The serum of patients with gastrointestinal bleeding who took clopidogrel (75 mg / d) for one year was isolated and placed in serum containing 5%, 10%, 15% and 20% respectively, The patient stopped using clopidogrel 10 days after the serum as a control. After incubation with GES-1 cells for 24 h, the cell morphology was observed by inverted phase contrast microscope. Cell proliferation and apoptosis were detected by MTT assay and flow cytometry respectively. Results: Compared with the control group, GES-1 cells were round and nuclear concentrated with different concentrations of drug-containing serum, which could inhibit proliferation and promote apoptosis of GES-1 cells in a concentration-dependent manner. Conclusion: The metabolites of clopidogrel after liver metabolism have an injury on human gastric mucosal epithelial cells.