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奥美拉唑致胃上皮凋亡及其机制的研究 被引量:11

Mechanism of omeprazole in inducing gastric epithelium apoptosis
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摘要 目的 探讨奥美拉唑致胃上皮凋亡及其作用机制。方法 采用流式细胞仪 ,测定奥美拉唑对SGC 790 1细胞株细胞周期、细胞凋亡发生的影响 ,并检测 p5 3、GADD4 5、p15 ,16 ,18,19和bcl 2的表达改变和ATP合酶活性。同时用TUNEL法检测奥美拉唑作用原代胃上皮细胞的凋亡情况。结果 奥美拉唑作用 2 4h引起SGC 790 1细胞周期发生显著改变 ,G1期百分比减少 ,G2 期百分比增加 ,以后者改变较明显 ,然无细胞凋亡峰出现 ,作用 72h出现细胞凋亡峰。p5 3、GADD4 5、p15 ,16 ,18,19和bcl 2表达均无显著改变 ,奥美拉唑作用前胞内ATP合酶活性为 0 .32 6~ 0 .387,奥美拉唑作用 72h后显著下降为 0 .0 5 4~ 0 .10 3。奥美拉唑致胃黏膜细胞凋亡发生率显著高于对照组 (P <0 .0 1)。结论 奥美拉唑通过线粒体途径导致胃上皮细胞凋亡 。 Objective To study whether omeprazole induces gastric epithelial cells apoptosis and analyse the possible mechanism. Methods The cell cycle and apoptosis ratio of SGC 7901 cell line were determined by flow cytometry in the presence of omeprazole, meanwhile, TUNEL positive cells from gastric mucosa were counted after incubated with omeprazole for 72 hours. Expression of p53、 GADD 45 、 p15,16,18,19 and bcl 2 were stained by immunohistochemical assay and ATPase activity was tested. Results significant alteration with decreasing percentage of G 1 phase and increasing percentage of G 2 phase of SGC 7901 cell line could be detected after incubating 24 hours with omeprazole at double clinical doses . An apoptosis peak appeared in flow cytometry after incubating 72 hours with omeprazole. However, no genetic products such as p53, GADD 45 , p15,16,18,19 and bcl 2 were seen. Concentrations of ATPase were markedly increased from 0.326 0.387 before incubated with omeprazole to 0.054 0.103 after incubated with omeprazole. TUNEL positive reaction cell counts in fresh mucosa was also increased after incubated with omeprazole for 72 hours( P <0.01). Conclusion Omeprazole could induce gastric epithelium cells apoptosis through mitochondria passway, which might play an importance role in repairing the gastric epithelium with oxidative DNA damage.
出处 《中华消化杂志》 CAS CSCD 北大核心 2001年第4期212-214,共3页 Chinese Journal of Digestion
关键词 奥美拉唑 细胞凋亡 线粒体 抗溃疡病药 Omeprazole Apoptosis Mitochondria
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