terlipressin对肝大部切除术后早期门静脉高灌注综合征的保护性治疗研究

The study of protective effect of terlipressin on portal hyperperfusion syndrome in the early phase of posthepatectomy

目的探讨terlipressin对大鼠肝大部切除术后再灌注早期门静脉高灌注综合征的保护性治疗作用及其机制。方法将36只大鼠随机分为特利加压素(terlipressin)治疗组(Th组,n=18)及生理盐水治疗对照组(Ch组,n=18)。两组大鼠分别在给药前及再灌注后30min,1h,2h4个时点进行血流动力学观察,并依此各再分为3亚组:Th1/2,Th1,Th2及Ch1/2,Ch1,Ch2组,每亚组6只大鼠。另20只大鼠随机分为特利加压素治疗存活组(Ts组)10只及生理盐水治疗存活对照组(Cs组)10只。采用肝大部切除术(90%)加肝门阻断(30min)动物模型,将Th组及Ts组大鼠在肝门阻断前通过阴茎背静脉注射terlipressin,Ch组及Cs组用同法在相同的时间给予同等体积的无菌生理盐水。观察terli-pressin对小体积肝大鼠生存率及血流动力学的影响。结果所有大鼠存活超过24h;Ts组10d存活率(80.0%)明显高于Cs组(30.0%)(P<0.05)。Th1/2亚组门静脉压力[(13.21±0.32)cmH2O]明显低于Ch1/2亚组的[(16±1.03)cmH2O](P<0.05);Th1亚组门静脉压力降到最低,达(11.52±0.17)cmH2O,明显低于Ch1亚组的(13.5±0.18)cmH2O(P<0.05)。与相对应组基础门静脉压力比较,Ch1/2亚组显著性增加(P<0.05)。Th1/2亚组门静脉血流[(7.21±0.21)mL/min]与Ch1/2亚组[(9.50±0.35)mL/min]比较,Th1亚组[(6.11±0.28)mL/min]与Ch1亚组[(6.99±0.19)mL/min]比较,差异均有统计学意义。同时,与相对应基础门静脉血流量比较,Ch1/2亚组显著增加(P<0.05)。Th1/2[(88.12±1.28)mmHg],Th1[(80.83±1.79)mmHg]及Th2[(76.29±0.89)mmHg]亚组平均动脉压明显高于相对应的Ch1/2[(57.97±2.01)mmHg],Ch1[(59.86±1.75)mmHg]及Ch2[(63.71±1.37)mmHg]亚组(均P<0.05)。Th1/2,Th1,Th2亚组亦显著高于相应的基础平均动脉压(均P<0.05)。两组各亚组之间及各组内每个亚组与基础中心静脉压比较差异无统计学意义。结论肝大部切除术后肝门静脉高灌注状态属一过性改变。terlipressin能有效缓解门静脉高灌注状态,可以降低门静脉压力及血流量,能显著提高肝大部切除术后小体积肝存活率。

Objective To explore the protective effect of terlipressin on portal hyperperfusion syndrome in the early phase of posthepateetomy. Methods Thirty-six rats were randomly categorized into two groups for the study of hemodynamics of portal hyperperfusion injury after hepatectomy ： 18 rats in Group Th （ terlipressin treatment group for hemodynamics ） and 18 rats in Group C （control group for hemodynamics ）. The hemodynamic parameters were detected before administration of terlipressin, and 30 min, 1 hour, and 2 hours after reperfusion. The Group T was subgrouped into subgroup Th1/2, Thl and Th2 group in terms of different timepoints, and the Group Ch was also subgrouped into subgroup Ch1/2, Ch1 and Ch2 group respectively. Each subgroup consisted of 6 rats. Twenty rats were randomly categorized into two groups for survival study ： 10 rats in Group Ts （ Terlipressin group for survival ） and 10 in Group Cs （ control group for survival）. All rats underwent major hepatectomy （90%） with Pringle maneuver for 30 minutes. Terlipressin was injected into the penile dorsal vein just before appliance of Pringle maneuver in rats of Group Th and Ts. The same amount of sterilized normal saline was injected at the same step in rats of Group Ch and Cs. The survival rate and hemodynamies of rats with small-for-size liver were studied. Results All rats survived more than 24 hours. The 10-day survival rate of Group Ts （80%） was significantly higher than that of Group Cs （ P 〈 0.05 ）. The portal pressure of subgroup Th 1/2 [ （ 13.21 ± 0.32 ） cm H2O ） ] was significantly lower than that of Subgroup Ch 1/2 [ （ 16 ± 1.03 ）em H2O ] （ P 〈 0.05 ）. The portal pressure reached its trough level [ （ 11.52 ± 0. 17 ） cm H2O ] in subgroup Th 1 , which was significantly lower than that in subgroup Chl [ （13.5 ±0. 18）cm H20] （P 〈 0. 05）. The portal pressure of subgroup Ch1/2 was significantly higher compared to its corresponding basic portal pressure （ P 〈 0. 05 ） . The portal blood flow of subgroup Th 1/2 [ （ 7.21 ± 0.21 ） mL/min ] and Th I [ （ 6.11± 0.28 ） mL/min ] was significantly lower than their corresponding subgroup Ch1/2 [ （9.50 ±0.35 ） mL/min] and Chl [ （6.99 ±0.19） mL/min ] （P 〈0.05）. Meanwhile, the portal blood flow of subgroup Ch1/2 was significantly higher compared to its corresponding basic portal blood flow （P 〈0. 05）. The mean blood pressure of subgroup Th1/2[（88. 12 ± 1. 28） mmHg ], Thl [ （ 80.83 ± 1.79 ） mmHg ] and Th2 [ （ 76.29 ± 0.89 ） mmHg ] was significantly higher than that of subgroup Ch1/2 [ （57.97 ± 2.01 ） mmHg ], Ch1 [ （59.86 ± 1.75 ） mmHgl and Ch2 [ （63.71 ± 1. 37 ） mmHg] （ P 〈 0.05 ） . Meanwhile, the mean blood pressure of subgroup Th1/2, Thl and Th2 was significantly higher than their corresponding basic mean blood pressure （ P 〈 0.05 ）. There was no significant difference of central venous pressure among all of the subgroups in Group Th and Group Ch. Also there was no significant difference of central venous pressure among all of the subgroups in each group compared to their corresponding basic central venous pressure. Conclusions Portal hyperperfusion state is transient in the early phase after major hepatectomy with reperfusion. Terlipressin ameliorates portal hyperperfusion injury by effectively reducing portal pressure and portal blood flow. The survival rate of rats with small-for-size liver after major hepateetomy can be significantly increased by administration of terlipressin.