南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (12): 1832-1838.doi: 10.12122/j.issn.1673-4254.2022.12.11

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乌司他丁联合右美托咪定对肝脏缺血再灌注损伤起保护作用：基于80例肝癌合并肝硬化行腹腔镜肝切除术患者

欧 毅，刘 刚，殷凤伟，杨 杨，张方圆   

  1. 蚌埠医学院第一附属医院麻醉科，安徽 蚌埠 233030
  • 出版日期:2022-12-20 发布日期:2023-01-12

Protective effect of ulinastatin combined with dexmedetomidine against hepatic ischemia-reperfusion injury in laparoscopic hepatectomy for liver cancer and cirrhosis: a randomized controlled trial

OU Yi, LIU Gang, YIN Fengwei , YANG Yang, ZHANG Fangyuan   

  1. Department of Anesthesiology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233030, China
  • Online:2022-12-20 Published:2023-01-12

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摘要： 目的 探讨乌司他丁联合右美托咪定对肝癌合并肝硬化患者行腹腔镜肝切除术（LH）缺血再灌注损伤（IRI）的保护作用。方法 择期行LH的肝癌合并肝硬化患者80例，随机分为U、D、UD和C 4组，每组20例。U组予以乌司他丁（1.0×104 U/kg），D组予以右美托咪定（负荷量0.5 μg/kg，持续10 min，然后以0.5 μg/（kg.h）维持至术毕前30 min），UD组予以乌司他丁联合右美托咪定处理，C组予以等容量0.9%氯化钠。于术前（T0）、术后30 min（T1）、术后24 h（T2）、术后3 d（T3）、术后5 d（T4）采集静脉血样。记录T0~T2时血清α-谷胱甘肽S-转移酶（α-GST）、丙二醛（MDA）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）浓度与T0和T2~T4时血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、尿素氮（BUN）和肌酐（Cr）浓度，并记录肝功能不全、并发症发生率和术后住院时间。结果 T1时，与C组比较，U组、D组和UD组血清α-GST、MDA、TNF-α和IL-6浓度明显降低（均P<0.05）；与UD组比较，U组和D组α-GST、MDA、TNF-α和IL-6浓度高于UD组（P<0.05）。T2时，与C组比较，U组、D组和UD组MDA、TNF-α和IL-6浓度明显降低（均P<0.05）；与UD组比较，U组和D组MDA、TNF-α和IL-6浓度高于UD组（均P<0.05）；而4组患者α-GST浓度差异无统计学意义（P>0.05）。T2~T4时，与C组比较，U组、D组和UD组ALT和AST浓度明显降低（均P<0.05）；与UD组比较，U组和D组ALT和AST浓度高于UD组。与C组比较，UD组术后住院时间明显缩短（P<0.05）。但4组患者术后肾功能、肝功能不全和并发症发生率差异无统计学意义（均P>0.05）。结论 乌司他丁联合右美托咪定可能通过协同抗氧化应激与抗炎反应，对肝脏IRI具有进一步的保护作用，从而减轻肝癌合并肝硬化患者围术期肝损伤，加速术后恢复。

关键词: 乌司他丁；右美托咪定；肝癌；肝硬化；腹腔镜肝切除术；缺血再灌注损伤

Abstract: Objective To investigate the protective effect of ulinastatin combined with dexmedetomidine against ischemia-reperfusion injury (IRI) of the liver in patients undergoing laparoscopic hepatectomy (LH) for liver cancer with cirrhosis. Methods Eighty patients with liver cancer and cirrhosis undergoing elective LH were randomized into ulinastatin (administered immediately before hepatectomy) group, dexmedetomidine (administered before anesthesia induction) group, ulinastatin plus dexmedetomidine group, and saline group (groups U, D, UD, and C, respectively). Venous blood samples were collected before the operation (T0) and at 30 min (T1), 24 h (T2), 3 days (T3), and 5 days (T4) after the operation. Serum levels of α-GST, MDA, TNF-α and IL-6 were analyzed at T0-T2. Serum levels of ALT, AST, BUN and Cr were measured at T0 and T2-T4, and the incidence of liver dysfunction, complications and postoperative hospital stay of the patients were recorded. Results At T1, serum α-GST, MDA, TNF-α and IL-6 levels increased significantly in groups U, D and UD compared with those in group C, and were significantly higher in groups U and D than in group UD (all P<0.05). At T2, the levels of MDA, TNF-α and IL-6 were significantly decreased in groups U, D and UD compared with those in group C, and were significantly higher in groups U and D than in group UD (all P<0.05). At T2-T4, the levels of ALT and AST were significantly lower in groups U, D and UD than in group C, and were higher in groups U and D than in group UD (all P<0.05). The patients in group UD had significantly shortened postoperative hospital stay as compared with those in group C (P<0.05). The incidences of complications or postoperative renal or liver insufficiency did not differ significantly among the 4 groups. However, there was no significant difference in the incidence of renal function, liver insufficiency and complications among the four groups (all P> 0.05). Conclusion In patients undergoing LH for liver cancer with cirrhosis, ulinastatin combined with dexmedetomidine provides enhanced protection against hepatic IRI possibly through a synergistic effect against oxidative stress and inflammatory response, thereby reducing perioperative liver injury and accelerating postoperative recovery

Key words: ulinastatin; dexmedetomidine; liver cancer; cirrhosis; laparoscopic hepatectomy; ischemia-reperfusion injury