解整合素-金属蛋白酶9在对乙酰氨基酚诱导的小鼠急性肝损伤中的表达分析
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摘要
目的研究解整合素-金属蛋白酶9(ADAM9)在对乙酰氨基酚诱导的小鼠急性肝损伤过程中的表达变化规律。方法 50只小鼠随机分为2组,正常组10只,实验组40只。实验组小鼠腹腔注射对乙酰氨基酚溶液550 mg·kg-1,6,24,42和72 h后分别摘除小鼠眼球采血、分离血清,同时分离正常组小鼠血清,检测谷草转氨酶和谷丙转氨酶活性;用蛋白印迹和反转录聚合酶链式反应(RT-PCR)等方法检测正常组小鼠和注射对乙酰氨基酚后不同时间点小鼠肝中ADAM9在蛋白和核酸水平的表达变化。结果对乙酰氨基酚注射小鼠后6 h,ADAM9的蛋白和核酸表达量显著下降(P<0.05),随着时间的延长,ADAM9的蛋白和核酸表达量继续下降,24 h达到最低值(P<0.05),然后随着肝损伤后的修复,ADAM9的表达量逐渐增加,在注射对乙酰氨基酚42 h后,ADAM9的蛋白和核酸表达量增加显著(P<0.05),72 h恢复到接近正常水平。结论 ADAM9在对乙酰氨基酚诱导的小鼠急性肝损伤过程中表达呈显著变化,ADAM9可能起到促进肝损伤后修复的重要作用。
Objective To study the expressed dynamic change and roles of a disintegrin and metalloprotease 9( ADAM9) during acute liver injury induced by acetaminophen. Methods Fifty mice were randomly divided into two groups: normal group( n = 10) and experiment group( n = 40).The mice in experiment group were respectively drawn blood by removing the eyeballs and serum was separated to detect the activity of aspartate aminotransferase( AST) and alanine aminotransferase( ALT) at 6,24,42 and 72 h after intraperitoneal injection of acetaminophen550 mg·kg- 1. The activity of serum AST and ALT in the mice of normal group were also detected. The expression of hepatic ADAM9 at protein and mRNA levels were detected by western blot and RT- PCR method in the mice of normal group and experiment group at different time points after acetaminophen injection. Results The expression of ADAM9 protein and mRNA were significantly down- regulated at 6 h( P < 0. 05),and the expression of ADAM9 protein and mRNA reached the lowest level at 24 h( P < 0. 05). After that,the expression of ADAM9 protein and mRNA were gradually increased. The expression of ADAM9 was significantly increased at 42 h( P < 0. 05),and then recoveredclosed to the normal level at 72 h after acetaminophen injection. Conclusion ADAM9 is remarkably differently expressed during acute liver injury induced by acetaminophen,which indicates that ADAM9 may play an important protective role during acute liver injury induce by acetaminophen in mice.
Objective To study the expressed dynamic change and roles of a disintegrin and metalloprotease 9( ADAM9) during acute liver injury induced by acetaminophen. Methods Fifty mice were randomly divided into two groups: normal group( n = 10) and experiment group( n = 40).The mice in experiment group were respectively drawn blood by removing the eyeballs and serum was separated to detect the activity of aspartate aminotransferase( AST) and alanine aminotransferase( ALT) at 6,24,42 and 72 h after intraperitoneal injection of acetaminophen550 mg·kg- 1. The activity of serum AST and ALT in the mice of normal group were also detected. The expression of hepatic ADAM9 at protein and mRNA levels were detected by western blot and RT- PCR method in the mice of normal group and experiment group at different time points after acetaminophen injection. Results The expression of ADAM9 protein and mRNA were significantly down- regulated at 6 h( P < 0. 05),and the expression of ADAM9 protein and mRNA reached the lowest level at 24 h( P < 0. 05). After that,the expression of ADAM9 protein and mRNA were gradually increased. The expression of ADAM9 was significantly increased at 42 h( P < 0. 05),and then recoveredclosed to the normal level at 72 h after acetaminophen injection. Conclusion ADAM9 is remarkably differently expressed during acute liver injury induced by acetaminophen,which indicates that ADAM9 may play an important protective role during acute liver injury induce by acetaminophen in mice.
引文
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[2]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.
[3]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.
[4]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.