右美托咪定对自体原位肝移植术大鼠肝缺血再灌注时程序性坏死的影响

Effect of dexmedetomidine on necroptosis during liverischemia-reperfusion in rats with autologous orthotopic liver transplantation

目的评价右美托咪定对自体原位肝移植术大鼠肝缺血再灌注时程序性坏死的影响。方法SPF级成年雄性SD大鼠24只,8~10周龄,体重250~280 g,采用随机数字表法分为3组(n=8):假手术组(S组)、自体原位肝移植组(T组)和右美托咪定组(D组)。T组和D组采用自体原位肝移植术制备大鼠肝移植术模型。D组术前30 min腹腔注射右美托咪定50μg/kg。于门静脉开放6 h(S组手术结束后6 h)取下腔静脉血样,测定血清AST、ALT、TNF-α和IL-10的水平;然后取大鼠肝组织标本,测定MD含量、SOD活性及受体相互作用蛋白1(RIP1)、受体相互作用蛋白3(RIP3)和混合系列蛋白酶样结构域(MLKL)的表达。结果与S组比较,T组与D组血清AST、ALT、TNF-α和IL-10的水平、肝组织MDA含量升高,SOD活性降低,RIP1、RIP3和MLKL的表达上调(P<0.05);与T组比较,D组血清AST、ALT和TNF-α的水平、肝组织MDA含量降低,肝组织SOD活性和血清IL-10浓度升高,肝组织RIP1、RIP3和MLKL的表达下调(P<0.05)。结论右美托咪定减轻自体原位肝移植术大鼠肝缺血再灌注损伤的机制与抑制程序性坏死有关。

Objective To evaluate the effect of dexmedetomidine on necroptosis during liver ischemia-reperfusion in rats with autologous orthotopic liver transplantation(AOLT).Methods Twenty-four SPF adult male Sprague-Dawley rats,aged 8-10 weeks,weighing 250-280 g,were divided into 3 groups(n=8 each)using a random number table method:sham operation group(group S),AOLT group(group T)and dexmedetomidine group(group D).The autologous orthotopic liver transplantation was performed in group T and group D.Dexmedetomidine 50μg/kg was intraperitoneally injected at 30 min before surgery in group D.Blood samples from the inferior vena cava were collected at 6 h after portal vein opening(6 h after the end of operation in group S)for determination of serum aspartate amino-transferase(AST),alanine amino-transferase(ALT),tumor necrosis factor-alpha(TNF-α)and interleukin-10(IL-10)levels.Liver specimens were obtained for determination of the malondialdehyde(MDA)content,superoxide dismutase(SOD)activity,and expression of receptor-interacting protein(RIP1),RIP3,and mixed lineage kinase domain-like(MLKL)in liver tissue.Results Compared with those in group S,the serum AST,ALT,IL-10 and TNF-αlevels,and MDA content of liver tissue significantly increased,the SOD activity decreased,and the expression of RIP1,RIP3 and MLKL was up-regulated in T and D groups(P<0.05).Compared with group T,the serum AST,ALT and TNF-αlevels,and MDA content of liver tissue significantly decreased,the SOD activity and serum IL-10 concentration increased,and the expression of RIP1,RIP3 and MLKL was down-regulated in group D(P<0.05).Conclusion The mechanism by which dexmedetomidine attenuates liver ischemia-reperfusion injury is related to inhibiting necroptosis in rats with AOLT.