异丙酚和川芎嗪相互作用对大鼠肝脏缺血/再灌注损伤的影响

目的采用正交设计试验方法探讨异丙酚与川芎嗪相互作用对大鼠肝脏缺血/再灌注损伤(HIRI)的影响。方法建立HIRI大鼠动物模型,按L32(45·216)正交表设计分组,缺血前20min,异丙酚用Graseby3500型微量泵经尾静脉持续输注,川芎嗪经尾静脉注射,等容量生理盐水用Graseby3500型微量泵经尾静脉持续输注,在阻断第一肝门前停止输注药物和液体。具体给药方案为Propofol:1(等量生理盐水)、2(5mg·kg-1·h-1)、3(10mg·kg-1·h-1)、4(20mg·kg-1·h-1),Ligustrazin:1(等量生理盐水)、2(15mg·kg-1)、3(30mg·kg-1)、4(60mg·kg-1)。大鼠组别:1(假手术组)、2(模型对照组),重复试验1次。检测血清ALT、AST值和肝组织匀浆上清液MDA、SOD值。结果模型对照组与假手术组比较HIRI大鼠血清ALT与AST水平升高(P<0·01);异丙酚与川芎嗪单独使用均能降低HIRI大鼠血清ALT与AST水平(P<0·05或P<0·01)。异丙酚与川芎嗪联用对降低HIRI大鼠血清的ALT存在交互作用(P<0·05),表现为协同效应。异丙酚与川芎嗪联用对降低HIRI大鼠肝组织匀浆上清液MDA存在交互作用(P<0·05),表现为协同效应。异丙酚与川芎嗪单独使用提高HIRI大鼠肝组织匀浆上清液SOD水平(P<0·05或P<0·01)。结论通过正交设计试验研究表明异丙酚与川芎嗪对大鼠HIRI具有明显的保护作用,作用机制可能通过其抗氧化作用实现,两者可能存在协同效应。

Effects of interaction between propofol and ligustrazin on hepatic ischemia-reperfusion injury in rat

Aim To investigate the effects of interaction between propofol and ligustrazin on hepatic ischemia-reperfusion injury (HIRI) by orthogonal design. Methods Sixty-four rats, male, weighing 241～289 g were randomly divided into group sham and group model of 32 animals each in the experiment. The hepatic ischemia was produced by clamping hepatic hilum for 30 min, and the hepatic reperfusion was allowed for 60 min after release of the clamp. The regimen of drugs followed as propofol:1 (same volume saline),2 (5 mg·kg~ -1 ·h~ -1 ),3 (10 mg·kg~ -1 ·h~ -1 ),4 (20 mg·kg~ -1 ·h~ -1 );ligustrazin:1(same volume saline),2 (15 mg·kg~ -1 ),3 (30 mg·kg~ -1 ),4 (60 mg·kg~ -1 ),groups of rat:1(group sham),2(group model).The propofol or the same volume of saline was infused by Graseby 3 500 micro-pump 20 min before hepatic ischemia; the ligustrazin was injected 20 min before hepatic ischemia. Blood samples were taken at 60 min after reperfusion for determination of ALT, AST concentration. Simultaneously liver tissue was taken in order to detect MDA content and SOD activities. Results The levels of serum ALT and AST were higher in group model than those in group sham (P<0.01). The levels of serum ALT and AST were reduced by either propofol or ligustrazin (P<0.05 or P<0.01). And the levels of serum ALT was significantly reduced by combination propofol and ligustrazin (P<0.05). The MDA content of liver tissue homogenate supernate was significantly reduced by combination propofol and ligustrazin (P<0.05). The SOD activity of liver tis- sue homogenate supernate was increased by propofol or ligustrazin respectively (P<0.05 or P<0.01). Conclusion Both propofol and ligustrazin have protective actions on hepatic ischemia reperfusion injury, which may be mediated by antioxidant way, and that the interaction between propofol and ligustrazin may strength these actions, and simultaneously they may exist effect of synergism.