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目的研究对乙酰氨基酚(AAP)诱导的小鼠药物性肝损伤过程中解整合素-金属蛋白酶8(ADAM8)表达的动态变化。方法健康雄性小鼠分别腹腔注射550 mg·kg-1AAP溶液,制备小鼠药物性肝损伤模型,在注射后6,24,42,72 h,分别眼球采血,分离血清;同时分离正常组小鼠血清,检测2组血清天冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶(ALT)活性;用蛋白印迹法和RTPCR法检测正常组小鼠和不同时间点的模型小鼠肝中ADAM8的表达变化。结果小鼠注射AAP后,血清中AST和ALT酶活呈先上升后下降的趋势。注射AAP6 h后,ADAM8的表达量显著上升(P<0.05),24 h达到最高峰(P<0.05),然后逐渐降低;至72 h又恢复到接近正常水平。结论 ADAM8在AAP诱导的小鼠药物性肝损伤过程中表达呈显著变化,可能起到促进肝损伤的重要作用。
Objective To investigate the dynamic changes of ADAM8 expression induced by paracetamol (AAP) induced drug-induced liver injury in mice. Methods Healthy male mice were injected intraperitoneally with 550 mg · kg-1AAP solution to prepare the model of drug-induced liver injury in mice. Blood samples were collected at 6, 24, 42 and 72 h after injection, respectively. Serum was also isolated from the normal mice Serum levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. Western blotting and RTPCR were used to detect the levels of serum ADAM8 expression changes. Results After AAP injection, AST and ALT activity in serum increased first and then decreased. After being injected with AAP for 6 h, the expression of ADAM8 increased significantly (P <0.05) and reached the peak at 24 h (P <0.05), then gradually decreased. At 72 h, ADAM8 returned to normal level. Conclusion The expression of ADAM8 in AAP-induced drug-induced liver injury is significantly changed, which may play an important role in promoting liver injury.