氯吡格雷对幽门螺杆菌感染小鼠胃黏膜ZO-1及IL-1β表达的影响

Effects of clopidogrel on the expression of ZO-1 and IL-1β in the gastric mucosa of mice infected with Helicobacter pylori

目的:研究氯吡格雷对幽门螺杆菌(Hp)感染小鼠胃黏膜损伤的影响及可能的损伤机制。方法:30只BALB/C雄性小鼠随机分为3组:对照组、Hp感染组、Hp感染+氯吡格雷组。制备Hp感染小鼠模型及氯吡格雷损伤胃黏膜的小鼠模型,4周后处死小鼠,观察各组小鼠胃黏膜大体变化,应用免疫组化法检测小鼠胃组织中紧密连接蛋白(zonula occludens-1,ZO-1)、白细胞介素-1β(IL-1β)的表达水平。结果:Hp感染组和Hp感染+氯吡格雷组小鼠胃黏膜大体损伤程度高于对照组(P<0.05),Hp感染+氯吡格雷组小鼠胃黏膜大体损伤程度高于Hp感染组(P<0.05);Hp感染组和Hp感染+氯吡格雷组小鼠胃组织IL-1β表达阳性率高于对照组(P<0.05),而ZO-1的表达阳性率低于对照组(P<0.05),Hp感染+氯吡格雷组小鼠胃组织IL-1β表达阳性率高于Hp感染组,ZO-1低于Hp感染组(P<0.05)。结论:氯吡幽格雷加重Hp感染小鼠胃黏膜的损伤,可能通过下调ZO-1在小鼠胃黏膜的表达破坏胃黏膜屏障,同时上调IL-1β参与炎症应答。

Objective ：To study the effects of clopidogrel on the gastric mucosa injury of Helicobacter pylori （Hp） infection in mice and the possible mechanisms of injury. Methods：30 male BALB/C mice were randomly divided into 3 groups： control group, Hp - infected group and Hp - infected ＋ clopidogrel group. The mice models of Hp infection and gastric mucosa injury by clopidogrel were set up. All mice were sacrificed after 4 weeks. The general changes of gastric mucosa tissue were observed, and immunohistochemistry was used to detect the expression of ZO - 1 and IL - 1β. Results： The degree of general gastric mucosa damage in experimental groups was higher than that in control group （ P 〈 0.05 ） , and the degree of general gastric mucosa damage in Hp - infected ＋ clopidogrel group was higher than that in Hp - infected group （ P 〈 0.05 ） ; The positive expression rates of IL - 1β on gastric tissue in experimental groups was higher than that in control group while the positive expression rates of ZO - 1 were lower than that in control group （ P 〈 0.05 ） ; The positive expression rate of IL - 1β on gastric tissue in Hp - infected ＋ clopidogrel group was higher than that in Hp - infected group, and the positive expression rate of ZO - 1 was lower than that in Hp - infected group （ P 〈 0. 05 ）. Conclusion ： Clopidogrel exacerbates the gastric mucosa injury in mice infected with Hp, damages the gastric mucosa barrier by decreasing the expression of ZO - 1 in gastric mucosa of mice, and gets involved in the inflammatory response by the up - regulation of IL - 1.