丙泊酚对大鼠移植肝NF-κB活化、ICAM-1、IL-1β和TNF-α表达的影响

Effects of propofol on the activity of NF-κB and expressions of TNF-α,IL-1β and ICAM-1 in transplanted liver of rats

目的探讨丙泊酚对供肝保护的机理。方法24只健康雄性SD大鼠,采用Kamada袖套法建立大鼠原位肝移植动物模型,随机均分为三组。移植肝再灌注前30min,P100组和P50组分别腹腔注射丙泊酚100mg/kg和50mg/kg;C组腹腔注射生理盐水15ml/kg作为对照。于肝脏再灌注6h抽取下腔静脉血,测定谷丙转氨酶(ALT)、谷草转氨酶(AST)活性,ELISA法测定肝组织核因子(NF)-κBp65转录因子,免疫组织化学染色检测肝组织细胞间黏附分子(ICAM)-1、白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α的表达。结果再灌注6h后,P100组、P50组大鼠血浆ALT、AST活性较C组明显降低(P<0.01);P50组ALT、AST活性较P100组增高(P<0.01)。与C组相比,P100组和P50组在再灌注6h大鼠肝组织NF-κBp65转录因子活化水平、TNF-α、IL-1β、ICAM-1mRNA明显降低(P<0.01)。P100组大鼠在再灌注6h肝组织NF-κBp65转录因子活化水平、TNF-α、IL-1β、ICAM-1mRNA表达明显低于P50组(P<0.01)。结论丙泊酚能抑制大鼠局灶性肝缺血-再灌注时NF-κB的活化,进而抑制炎症反应。这可能是其肝保护作用的机制之一。

Objective To investigate the possible mechanism of propofol in protecting the function of translated liver. Methods After establishment of orthotopic liver transplantation（OLT） model with Kamada method,24 male SD rats were randomly divided into 3 groups with 8 rats each. The rats in groups of P100 and Ps0 were given propofol 100 mg/kg and 50 mg/kg, respectively, at 30 min before reperfusion of the transplanted liver, and those in group C were injected normal saline 15 ml/kg as the controls. Blood samples and liver tissues were obtained at 6 h after liver transplantation for detecting plasma ALT and AST activity. The activity of nuclear factor（NF）-κB p65 was detected by ELISA , and interleukin-1β（IL-1β）, tumor necrosis factor-α （TNF-α） and intercellular adhesion molecule-1 （ICAM-1） in liver tissues were detected by immunohistochemical staining. Results Following reperfusion for 6 h, the activities of ALT and AST were lower in groups of P100 and P50 than those in group C（P〈0. 01 ）, which were higher in group P50 than those in group Pl00 （P〈0. 01）. Compared to group C, the activity of NF-κB and the expressions of TNF-α, IL-1β and ICAM-1 mRNA in liver tissues were markedly lower in groups of P100 and Pa0 than those in group C（P〈0. 01）,which were lower in group P100 than those in group P50 （P〈0.01）. Conclusion Propofol inhibits the inflammatory reaction by inhibiting NF-κB activation during focal liver ischemia-reperfusion injury, which may be one of the mechanisms for its protective effect on liver function.