中国临床药理学杂志
中國臨床藥理學雜誌
중국림상약이학잡지
THE CHINESE JOURNAL OF CLINICAL PHARMACOLOGY
2014年
10期
926-928
,共3页
李三强%崔旭红%杨兰泽%马曌%韩红梅
李三彊%崔旭紅%楊蘭澤%馬曌%韓紅梅
리삼강%최욱홍%양란택%마조%한홍매
对乙酰氨基酚%解整合素 -金属蛋白酶 8%药物性肝损伤%蛋白表达
對乙酰氨基酚%解整閤素 -金屬蛋白酶 8%藥物性肝損傷%蛋白錶達
대을선안기분%해정합소 -금속단백매 8%약물성간손상%단백표체
acetaminophen%a disintegrin and metalloprotease 8%drug -induced liver injury%protein expression
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-1 AAP 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 RT -PCR 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。
目的：研究對乙酰氨基酚（AAP）誘導的小鼠藥物性肝損傷過程中解整閤素-金屬蛋白酶8（ADAM8）錶達的動態變化。方法健康雄性小鼠分彆腹腔註射550 mg? kg-1 AAP 溶液，製備小鼠藥物性肝損傷模型，在註射後6，24，42，72 h，分彆眼毬採血，分離血清；同時分離正常組小鼠血清，檢測2組血清天鼕氨痠氨基轉移酶（AST）和丙氨痠氨基轉移酶（ALT）活性；用蛋白印跡法和 RT -PCR 法檢測正常組小鼠和不同時間點的模型小鼠肝中 ADAM8的錶達變化。結果小鼠註射 AAP 後，血清中 AST 和 ALT 酶活呈先上升後下降的趨勢。註射 AAP6 h 後， ADAM8的錶達量顯著上升（ P ＜0．05），24 h 達到最高峰（P ＜0．05），然後逐漸降低；至72 h 又恢複到接近正常水平。結論ADAM8在 AAP 誘導的小鼠藥物性肝損傷過程中錶達呈顯著變化，可能起到促進肝損傷的重要作用。
목적：연구대을선안기분（AAP）유도적소서약물성간손상과정중해정합소-금속단백매8（ADAM8）표체적동태변화。방법건강웅성소서분별복강주사550 mg? kg-1 AAP 용액，제비소서약물성간손상모형，재주사후6，24，42，72 h，분별안구채혈，분리혈청；동시분리정상조소서혈청，검측2조혈청천동안산안기전이매（AST）화병안산안기전이매（ALT）활성；용단백인적법화 RT -PCR 법검측정상조소서화불동시간점적모형소서간중 ADAM8적표체변화。결과소서주사 AAP 후，혈청중 AST 화 ALT 매활정선상승후하강적추세。주사 AAP6 h 후， ADAM8적표체량현저상승（ P ＜0．05），24 h 체도최고봉（P ＜0．05），연후축점강저；지72 h 우회복도접근정상수평。결론ADAM8재 AAP 유도적소서약물성간손상과정중표체정현저변화，가능기도촉진간손상적중요작용。
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 remo -ving the eyeballs and serum was separated to detect the activity of aspar -tate aminotransferase (AST) and alanine aminotranferease (ALT) at 6, 24, 42 and 72 h after intraperitoneal injection with 550 mg? kg-1 AAP. 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.
