解整合素-金属蛋白酶8在小鼠药物性肝损伤中的表达
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摘要
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 study the expressed dynamic change and roles of a disintegrin and metalloprotease 8( ADAM8) during drug- induced liver injury induced by acetaminophen( AAP). Methods Mice were randomly divided into two groups: normal group and experimental group.The mice in experimental group were respectively drawn blood by removing the eyeballs and serum was separated to detect the activity of aspartate aminotransferase( AST) and alanine aminotranferease( ALT) at 6,24,42 and 72 h after intraperitoneal injection with 550 mg·kg- 1AAP.The activity of serum AST and ALT in the mice of normal group was also detected. The expression of hepatic ADAM8 at protein and mRNA levels was detected by Western blot and RT- PCR in the mice of normal group and experimental group at different time points after AAP injection.Results Serum AST and ALT activity was first increased and then decreased after AAP injection in the mice. The expression of ADAM8 were significantly up- regulated( P < 0. 05) at 6 h,reached peak level at 24 h( P < 0. 05). Then gradually down- regulated and recovered near the normal level at 72 h after AAP injection. Conclusion ADAM8 were remarkably differently expressed during drug- induced liver injury induced by AAP,which may play an important role in promoting liver damage during drug- induced liver injury induced by AAP.
Objective To study the expressed dynamic change and roles of a disintegrin and metalloprotease 8( ADAM8) during drug- induced liver injury induced by acetaminophen( AAP). Methods Mice were randomly divided into two groups: normal group and experimental group.The mice in experimental group were respectively drawn blood by removing the eyeballs and serum was separated to detect the activity of aspartate aminotransferase( AST) and alanine aminotranferease( ALT) at 6,24,42 and 72 h after intraperitoneal injection with 550 mg·kg- 1AAP.The activity of serum AST and ALT in the mice of normal group was also detected. The expression of hepatic ADAM8 at protein and mRNA levels was detected by Western blot and RT- PCR in the mice of normal group and experimental group at different time points after AAP injection.Results Serum AST and ALT activity was first increased and then decreased after AAP injection in the mice. The expression of ADAM8 were significantly up- regulated( P < 0. 05) at 6 h,reached peak level at 24 h( P < 0. 05). Then gradually down- regulated and recovered near the normal level at 72 h after AAP injection. Conclusion ADAM8 were remarkably differently expressed during drug- induced liver injury induced by AAP,which may play an important role in promoting liver damage during drug- induced liver injury induced by AAP.
引文
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[2]Schwettmann L,Wehmeier M,Jokovic D,et al.Hepatic expression of A disintegrin and metalloproteinase(ADAM)and ADAMs with thrombospondin motives(ADAM-TS)enzymes in patients with chronic liver diseases[J].J Hepatol,2008,49:243-250.
[3]Marolda R,Ciotti MT,Matrone C,et al.Substance P activates ADAM9 mRNA expression and inducesα-secretase-mediated amyloid precursor protein cleavage[J].Neuropharmacology,2012,62:1954-1963.
[4]Guaiquil VH,Swendeman S,Zhou W,et al.ADAM8 is a negative regulator of retinal neovascularization and of the growth of heterotopically injected tumor cells in mice[J].J Mol Med,2010,88:497-505.
[5]Li SQ,Li RF,Xi SM,et al.Systematical analysis of impacts of heat stress on the proliferation,apoptosis and metabolism of mouse hepatocyte[J].J Physiol Sci,2012,62:29-43.
[6]马英剑,李三强.HSP70在对乙酰氨基酚诱导的小鼠急性肝损伤组织中的表达[J].河南科技大学学报(医学版),2012,30:8-9.
[7]Ishikawa N,Daigo Y,Yasui W,et al.ADAM8 as a novel serological and histochemical marker for lung cancer[J].Clin Cancer Res,2004,10:8363-8370.