氯吡格雷对幽门螺旋菌感染小鼠胃黏膜损伤的研究

Research of gastric mucosa injury induced by clopidogrel in mice with helicobacter pylori infection

目的探讨氯吡格雷是否加重幽门螺旋菌(Hp)感染小鼠胃黏膜损伤及其损伤机制。方法将40只雄性小鼠随机分为实验组、对照A组、对照B组和空白组,每组10只。4组小鼠均先给予2%碳酸氢钠溶液灌胃,每只0.2 mL;0.5 h后,空白组和对照A组均给予0.9%NaCl灌胃,每只0.5 mL,对照B组和实验组均给予Hp细菌悬液灌胃,每只0.5 mL;4组小鼠每天1次,连续给药10 d。3周后,4组小鼠均先给予2%碳酸氢钠溶液灌胃,每只0.2 mL,0.5 h后,对照A组和实验组均给予氯吡格雷混悬液灌胃,每只0.5 mL,空白组和对照B组均给予0.9%NaCl灌胃,每只0.5 mL;每天1次,连续给药1周。4周后处死小鼠,用蛋白免疫印迹法观察Occludin蛋白相对表达量,用逆转录聚合酶链反应法观察Occludin mRNA的表达水平。结果实验组、对照A组、对照B组和空白组的Occludin蛋白相对表达量分别为0.43±0.12,1.02±0.25,1.05±0.28和1.76±0.27,Occludin mRNA表达量分别为0.78±0.17,1.21±0.16,1.19±0.16和1.83±0.35,实验组的上述指标均显著低于对照A组和对照B组,差异均有统计学意义(均P<0.05)。结论氯吡格雷可加重Hp感染小鼠胃黏膜损伤。氯吡格雷及Hp感染小鼠胃黏膜损伤可能与Occludin蛋白表达下降相关。氯吡格雷可使Hp感染小鼠胃黏膜Occludin蛋白表达进一步下降,从而加重小鼠胃黏膜损伤。

Objective To investigate whether clopidogrel aggravates gastric mucosal injury and its mechanism in mice infected with helicobacter pylori(Hp). Methods A total of 40 male mice were randomly divided into experimental group, control A group, control B group and blank group with 10 cases per group. The mice in four groups were given 2% sodium bicarbonate solution by gavage, 0.2 mL per mice;after 0.5 h, the blank group and control A group were given 0.9%NaCl 0.5 mL per mice, control B group and experimental group were given HP bacterial suspension by gavage, 0.5 mL per mice;four groups were treated for 10 days with once a day. Three weeks later, the mice in four groups were given 2% sodium bicarbonate solution by gavage, 0.2 mL per mice, after 0.5 h, control A group and experimental group were given clopidogrel suspension by gavage, 0.5 mL per mice, blank group and control B group were given 0.9%NaCl 0.5 mL per mice;four groups were treated for 1 week with once a day. After 4 weeks,all mice were killed,the relative expression of Occludin protein was observed by Western-Blot method,the expression of Occludin mRNA was observed by reverse transcription-polymerase chain reaction method. Results The relative expression levels of Occludin protein in experimental,control A,control B and blank groups were 0. 43 ± 0. 12,1. 02 ± 0. 25,1. 05 ± 0. 28 and 1. 76 ± 0. 27,the expression levels of Occludin mRNA were 0. 78 ± 0. 17,1. 21 ± 0. 16,1. 19 ± 0. 16 and 1. 83 ± 0. 35. The above-mentioned indexes in the experimental group were significantly lower than those in control A and control B groups,and the differences were statistically significant( all P < 0. 05). Conclusion Clopidogrel can aggravate gastric mucosal injury in Hp-infected mice. The gastric mucosal injury induced by clopidogrel in Hp-infected mice may be related to the decreased expression of Occludin protein. Clopidogrel can further reduce the expression of Occludin protein in gastric mucosa of Hp-infected mice,which aggravated the gastric mucosal injury in mice.