氯胺酮对烧伤早期小鼠肝应激相关蛋白IFIT1和JAB1表达的影响

Effect of ketamine on the expression of hepatic stress protein IFIT1 and JAB1 during the early stage of burns in mice

目的：观察小鼠应激相关蛋白IFIT1（Interferon-induced protein with tetratricopetide repeats1）和JAB1（c-Jun平activation共处五项原则domain-binding protein 1）在肝脏的表达的细胞定位及氯胺酮对烧伤后早期肝脏IFIT1和JAB1表达的影响，初步探讨氯胺酮调节炎症反应的分子机制。方法：将15只健康C57／129小鼠随机分为3组（n=5），正常对照组、烧伤组、烧伤＋氯胺酮组。采用TBSA 15～20％Ⅲ度小鼠烧伤模型；氯胺酮10mg／kg，肌肉注射，烧伤15min给予。分别于烧伤后4h脱臼处死，取肝。采用免疫印迹法（Western blot）察各组肝IFIT1和JAB1的表达情况。取正常对照组肝组织作病理切片，行免疫组织化学方法对IFIT1和JAB1的表达做细胞定位。结果：烧伤组IFIT1表达较正常对照组显著增高（P〈0．01）．烧伤组JAB1表达较正常对照组显著降低（P〈0．01）：氯胺酮治疗组IFIT1表达较正常对照组、烧伤对照组显著降低（P〈0．01）．氯胺酮治疗组JAB1表达较正常对照组显著降低（P〈0．05）、较烧伤组显著升高（P〈0．05）。免疫组织化学方法显示．IFIT1在肝细胞胞浆表达为阳性．JAB1在肝细胞胞浆和胞核均表达为阳性。结论：烧伤早期小鼠肝组织IFIT1表达增高而JJAB1表达降低，氯胺酮可降低烧伤早期小鼠肝组织IFIT1的高表达，增高JAB1表达；氯胺酮可通过调控严重烧伤应激中IFIT1和JAB1的表达而在全身炎性反应综合症（Systemic inflammatory response syndrome SIRS）中发挥作用。

Objective：To evaluate the effect of ketamine on the expression level of hepatic stress protein IFIT1 and JAB1 during the early stage of burns in mice, and observe the location of IFIT1 and JAB1 in hepatic cells. Methods：15 C57/129 male mice were divided randomly into three groups（n=5）： normal control,burns,burns＋ketamine. Burns group and burns＋ketamine group were inflicted with 15%-20% TBSA full thickness burn injury,and burns＋ketamine group received an intramuscular injection of 10 mg/kg ketamine 15 min after burns. At 4 h after burns,hepatic tissue was taken from mice,and the levels of hepatic I- FIT1 and JAB1 were detected by western blot. Normal control hepatic pathological section was taken; then cell location of I- FIT1 and JAB1 was detected by immunohistochemistry. Results：In burns group, the expression level of hepatic IFIT1 significantly increased, while that of JAB1 decreased as compared with normal control（P〈0.01）. In Burns＋ketamine group, the expression level of IFIT1 significantly decreased as compared with normal control and burns group（P〈0.01）,but in Burns＋ketamine group JAB1 significantly decreased as compared with normal control（P〈0.05）,but significantly increased as compared with burns group（P〈0.05）. Conclusion：These results indicate that the expression of IFIT1 increases and JAB1 decreases during the early stage of burns in the liver. Ketamine could not directly effect inflammatory reaction, but it could suppress these changes of I- FIT1 and JAB1 to play a role in systemic inflammatory response syndrome（SIRS）.