CAJ | 학술논문

目的：研究重度创伤性脑损伤（TBI）诱导的应激性肝损害（HSI）大鼠肝组织细胞色素 P4502El （CYP2E1）的变化。方法取40只健康雄性 Wistar 大鼠，随机分为假手术(A 组)和 TBI 组，采用改良的 Feeney 自由落体撞击法建立 TBI 大鼠模型；于颅脑致伤后6、12和24 h，检测各组血清 ATL、AST 水平和丙二醛（MDA）水平变化，在光镜下观察肝脏组织学改变，采用 RT-PCR 和 Western blot 法分别检测各组肝组织 CYP2E1 mRNA 和蛋白表达。结果在 TBI 后6和24 h，各组大鼠血清 ALT 较基线水平[（42.2±8.1） U/L]明显升高[分别为（83.0±10.3） U/L 和（1204.5±146.6） U/L，P<0.01）]；伤后12 h 血清 AST 较基线[（44.0±7.2） U/L]升高[（280.4±53.3） U/L，P<0.01）]，于24 h 达峰值[（790.3±114.5） U/L]；伤后6 h MDA 较基线[（5.2±0.2） nmol/mg]明显升高[（14.2±0.2） nmol/mg，P<0.05]，24 h 达峰值[（56.3±0.5） nmol/mg]；伤后24 h 肝组织损伤最严重，可见肝小叶结构不清，肝窦明显扩张，散在肝细胞点状坏死，大量炎细胞浸润；伤后6 h 肝组织 CYP2E1 mRNA 和蛋白表达水平较基线水平[分别为（0.28±0.02）和（61.68±0.60）]明显增加[（0.89±0.05）和（120.24±1.22），P<0.05]，在24 h 达峰值[分别为（1.50±0.02）和（200.40±2.61），P<0.01]。结论 CYP2E1可能参与了 TBI 诱导的氧化应激反应，从而引起 HSI。
목적：연구중도창상성뇌손상（TBI）유도적응격성간손해（HSI）대서간조직세포색소 P4502El （CYP2E1）적변화。방법취40지건강웅성 Wistar 대서，수궤분위가수술(A 조)화 TBI 조，채용개량적 Feeney 자유락체당격법건립 TBI 대서모형；우로뇌치상후6、12화24 h，검측각조혈청 ATL、AST 수평화병이철（MDA）수평변화，재광경하관찰간장조직학개변，채용 RT-PCR 화 Western blot 법분별검측각조간조직 CYP2E1 mRNA 화단백표체。결과재 TBI 후6화24 h，각조대서혈청 ALT 교기선수평[（42.2±8.1） U/L]명현승고[분별위（83.0±10.3） U/L 화（1204.5±146.6） U/L，P<0.01）]；상후12 h 혈청 AST 교기선[（44.0±7.2） U/L]승고[（280.4±53.3） U/L，P<0.01）]，우24 h 체봉치[（790.3±114.5） U/L]；상후6 h MDA 교기선[（5.2±0.2） nmol/mg]명현승고[（14.2±0.2） nmol/mg，P<0.05]，24 h 체봉치[（56.3±0.5） nmol/mg]；상후24 h 간조직손상최엄중，가견간소협결구불청，간두명현확장，산재간세포점상배사，대량염세포침윤；상후6 h 간조직 CYP2E1 mRNA 화단백표체수평교기선수평[분별위（0.28±0.02）화（61.68±0.60）]명현증가[（0.89±0.05）화（120.24±1.22），P<0.05]，재24 h 체봉치[분별위（1.50±0.02）화（200.40±2.61），P<0.01]。결론 CYP2E1가능삼여료 TBI 유도적양화응격반응，종이인기 HSI。
Objective To explore the dynamic changes of cytochrome P4502El(CYP2E1)in liver tissues of rats with hepatic stress injury (HSI) secondary to traumatic brain injury (TBI). Methods Forty healthy male Wistar rats were randomly divided into sham-operated and TBI group. The animal model was established by an improved Feeney method. Serum levels of ALT and AST were measured by enzymatic assay at 6,12 and 24 h after TBI;MDA contents in liver tissues were also measured. Pathological changes of liver tissues were observed under light microscopy. The CYP2E1 mRNA levels and its protein expression were detected by RT-PCR and Western blot,respectively. Results At 6 h and 24 h after TBI,serum ALT elevated significantly [(83.0±10.3)U/L and(1204.5±146.6) U/L,respectively,P﹤0.01)] as compared with baseline [(42.2±8.1) U/L];at 12 h after TBI, serum AST elevated significantly [(280.4±53.3) U/L,P﹤0.01)] compared with baseline [(44.0±7.2)) U/L],and it peaked at 24 h[(790.3±114.5) U/L];at 6 h after TBI,serum MDA elevated significantly [(14.2±0.2)nmol/mg,P﹤0.05] compared with baseline[(5.2±0.2)nmol/mg],and it peaked at 24 h after TBI [(56.3±0.5)nmol/mg];at 24 h after TBI,the injuries in liver tissues were serious,with expanded sinus,scattered spotty necrosis and inflammatory cell infiltration;at 6 h after TBI,both mRNA and protein levels of CYP2E1 were significantly elevated [(0.89± 0.05)and (120.24±1.22),P﹤0.05] compared with baseline [(0.28±0.02) and (61.68±0.60),respectively],and they peaked at 24 h after TBI [(1.50±0.02)and (200.40±2.61),respectively,P﹤0.01]. Conclusions CYP2E1 may be involved in oxidative stress in hepatic stress injury after TBI.