不同剂量利多卡因对脓毒症大鼠急性肝损伤的影响

Effects of different doses of lidocaine on acute liver injury in septic rats

目的评价不同剂量利多卡因对脓毒症大鼠急性肝损伤的影响。方法健康清洁级雄性Wistar大鼠50只，体重200～250g，8～10周龄，采用随机数字表法将大鼠随机分为5组（n=10）：假手术组（s组）、模型组（CLP组）、不同剂量利多卡因组（L1-3组）。采用盲肠结扎穿孔（CLP）法制备脓毒症模型。于CLP术后即刻、1、2h时s组和CLP组分别腹腔注射生理盐水0．5ml，L1-3，组分别腹腔注射利多卡因5、10和20mg／kg。于术后24h时采集血样测定血浆谷丙转氨酶（ALT）活性，处死后取肝组织检测高迁移率族蛋白1（HMGB1）mRNA表达水平，光镜下观察肝组织病理学改变。结果与s组比较，其余各组血浆ALT浓度升高，肝组织HMGB1mRNA表达上调（P〈0．05）。与CLP组比较，L1-3组肝组织HMGB1mRNA表达下调，L2组和L3组血浆ALT浓度降低（P〈0．05）。与L1组比较，L2组和L3组血浆ALT浓度降低，肝组织HMGB1mRNA表达下调（P〈0．05）。与L2组比较，L3组血浆ALT浓度降低，肝组织HMGB1mRNA表达下调（P〈0．05）。CLP组肝组织病理损伤严重，L1-3组肝组织病理损伤均减轻，且L3组最为明显。结论利多卡因可减轻脓毒症大鼠急性肝损伤，且与剂量有关，其机制与抑制肝组织HMGB1mRNA过表达有关。

Objective To investigate the effects of different doses of lidocaine on acute liver injury in septic rats.Methods Fifty male Wistar rats, weighing 200-250 g, aged 8-10 weeks, were randomly divided into 5 groups （n = 10 each） ： sham operation group （group S）, sepsis group （group CLP）, and different doses of lidocaine groups （groups L1-3）. Sepsis was induced by cecal ligation and puncture （CLP） in anesthetized rats. At 0, 1 and 2 h after CLP, lidocaine 5, 10 and 20 mg/kg （in normal saline 0.5 ml） were injected intraperitoneally in groups L1-3 respectively, while normal saline 0.5 ml was given in groups S and CLP. At 24 h after CLP, blood samples were taken for determination of the plasma alanine aminotransferase （ALT） concentration. The rats were then sacrificed, and the liver was removed for microscopic examination and determination of the hepatic high-mo- bility group box 1 protein （HMGB1） mRNA expression. Results Compared with group S, the plasma ALT concentration was significantly increased and hepatic HMGB1 mRNA expression was up-regulated in groups CLP and L1-3 （P 〈 0.05）. Compared with group CLP, HMGB1 mRNA expression was down-regulated in groups L1-3 , while the plasma ALT concentration was decreased in groups L2 and L3 （P 〈 0.05）. The plasma ALT concentration was significantly decreased and HMGB1 mRNA expression was down-regulated in groups L2 and L3 compared with group L1 , and in group L3 compared with group L2 （ P 〈 0.05）. The microscopic examination showed that the pathologic changes were attenuated in groups L1-3, and the changes were least severe in group L3 . Conclusion Lidocaine can reduce acute liver injury in septic rats, this effect is dose-related, and inhibition of hepatic HMGB1 mRNA expression is involved in the mechanism.