实用医学杂志 ›› 2021, Vol. 37 ›› Issue (20): 2602-2607.doi: 10.3969/j.issn.1006⁃5725.2021.20.007

• 基础研究 • 上一篇    下一篇

米诺环素抑制5-脂氧合酶对未控制失血性休克大鼠肝组织的保护作用

郑强1 温天明1 舒其琛1 杨虎1 翟祥龙1 刘世平2   

  1. 1 成都市第一人民医院急诊科(成都 610000);2 川北医学院附属医院急诊科(四川南充 637000)


  • 出版日期:2021-10-25 发布日期:2021-10-25
  • 通讯作者: 刘世平 E⁃mail:liusp456@163.com
  • 基金资助:
    四川省教育厅重点项目(编号:13ZA0219);四川省卫生和计划生育委员会重点研究项目(编号:17ZD016)

Minocycline inhibits 5 ⁃ lipoxygenase to protect the liver tissue of rats with uncontrolled hemorrhagic
shock

ZHENG Qiang*,WEN Tianming,SHU Qichen,YANG Hu,ZHAI Xianglong,LIU Shiping.   

  1. Department of Emergency,Chengdu First People′s Hospital,Chengdu 610000,China

  • Online:2021-10-25 Published:2021-10-25
  • Contact: LIU Shiping E⁃mail:liusp456@163.com

摘要:

目的 探讨米诺环素通过抑制 5-脂氧合酶对未控制失血性休克大鼠肝组织的保护作用。 方法 SD 大鼠麻醉置管成功后分为 4 组:假手术组(空白组)10 只,液体复苏组(对照组)10 只,MK⁃886 治疗组(实验组 1)10 只,米诺环素治疗组(实验组 2)10 只。置管成功后制备未控制失血性休克模型;Elisa 法检测血 3.5 h TNF⁃α、IL⁃6、肝组织 LTs、LTB4 5⁃LOX;比色法和 TBA 法分别检测肝组织丙二醛(MDA)、 髓过氧化物酶(MPO),并分析病理切片;全自动生化分析仪检测血 3.5 h 谷丙转氨酶(ALT)、谷草转氨酶 AST)水平。结果 实验组 1 与实验组 2 的死亡率及补液量明显低于对照组,实验组 2 的死亡率及补液量 低于实验组 1。实验组 2 TNF⁃α、IL⁃6 值明显低于实验组 1 与对照组(P < 0.05),实验组 1 与实验组 2 肝功能 ALT、AST)比较,差异无统计学意义(P > 0.05),实验组 1 与对照组比较差异有统计学意义(P < 0.05)。实验组 1 与实验组 2 肝脏组织 LTs、LTB4、5⁃LOX 值明显低于对照组(P < 0.05);且实验组 1 与实验组 2 比较差 异无统计学意义(P > 0.05)。对照组肝组织 MDA MPO 值均高于实验组 1 及实验组 2(P < 0.05);实验组 1 肝脏组织 MDA MPO 值与实验组 2 肝脏组织 MDA MPO 值相近(P > 0.05),但低于对照组。实验组 1 与实验组 2 的肝脏组织病理切片损伤程度较对照组轻(P < 0.05);且实验组 1 与实验组 2 Suzuki′s 评分 比较差异无统计学意义(P > 0.05)。结论 在未控制失血性休克模型中 MC 可能通过抑制 5⁃LOX 发挥抗 炎作用,进而抑制 TNF⁃α、IL⁃6、LTs、LTB4、MAD MPO 等炎症介质和细胞因子,减轻缺血再灌注后肝组织 和细胞损伤,发挥肝组织的保护作用,降低死亡率。

关键词:

Abstract:

Objective Minocycline has been shown to be protective on liver injury in uncontrolled hemor⁃ rhagic shock models,but the specific mechanism is not fully understood. Methods After anesthesia and catheter⁃ ization,SD rats were divided into 4 groups:sham operation group(blank group),fluid resuscitation group(con⁃ trol group),MK ⁃ 886 treatment group(experimental group 1),and minocycline treatment group(experimental group 2). Uncontrolled hemorrhagic shock model was prepared after successful catheterization. ELISA was used to detect TNF⁃α at 3.5h,IL⁃6,LTS,LTB4 and 5⁃LOX;Malondialdehyde(MDA)and myeloperoxidase(MPO)in liver tissue were analyzed and the pathological section was prepared. Automatic biochemical analyzer was used to detect the liver function for 3.5 h:alanine aminotransferase(ALT)and aspartate aminotransferase(AST). Results The mortality and fluid replacement volume of experimental group 1 and 2 were significantly lower than those of control group,and the mortality and fluid replacement volume of experimental group 2 were lower than those of experimental group 1. The values of TNF⁃α and IL⁃6 in experimental group 2 were significantly lower than those in experimental group 1 and control group(P < 0.05). The values of liver function(ALT and AST)in experi⁃ mental group 1 and experimental group 2 were significantly lower than those in experimental group 1 and control group(P < 0.05). The values of LTS,LTB4 and 5⁃LOX in liver tissue of experimental group 1 and experimental group 2 were significantly lower than those of control group(P < 0.05). Compared with experimental group 2,MDA and MPO of liver and tissue in control group were higher than those in experimental group 1 and 2(P < 0.05;The values of MDA and MPO in liver tissue of experimental group 1 were similar to those of experimental group 2 (P > 0.05),but lower than those of control group. The degree of liver tissue injury in experimental group 1 and experimental group 2 was less than that in control group. There was no significant difference in the Suzuki′ s score of experimental group 1 was compared with that of experimental group 2(P > 0.05). Conclusions In uncon⁃ trolled hemorrhagic shock models,MC may play an anti⁃inflammatory role by inhibiting 5⁃LOX,and then inhibit inflammatory mediators and cytokines such as TNF⁃α,IL⁃6,LTS,LTB4,MAD and MPO,so as to reduce liver tissue and cell damage after ischemia and reperfusion and play a protective role in liver tissue.

Key words:

minocycline, 5?LOX, hemorrhagic shock, liver