丙泊酚对二氧化碳气腹大鼠肝功能及HMGB1/TLR4信号通路的影响

doi:10.3969/j.issn.1006-6233.2022.04.03

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摘要 目的:探讨丙泊酚对二氧化碳气腹大鼠肝功能及肝组织高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)通路的影响。方法:通过设置气腹压力20mmHg持续2h建立气腹模型大鼠,将造模成功大鼠随机分为气腹组、丙泊酚低(5mg/kg)、中(10mg/kg)、高(20mg/kg)剂量组、阳性对照组(联苯双酯,25mg/kg),每组10只;另外设假手术组(10只健康大鼠,只进行造模手术,不建立气腹)。术后2h给药,假手术组和气腹组经腹腔注射生理盐水,丙泊酚各剂量组经腹腔注射相应剂量丙泊酚溶液,阳性对照组灌胃给予联苯双酯溶液。给药后10h,取大鼠腹主动脉血及肝组织,酶联免疫吸附法检测肝功能指标血清天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)及肝组织炎症因子白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平,苏木精-伊红染色检测大鼠肝组织形态变化,蛋白免疫印迹法检测肝组织HMGB1、TLR4、单核细胞趋化蛋白-1(MCP-1)、细胞间黏附分子-1(ICAM-1)、干扰素-γ(IFN-γ)蛋白表达情况。结果:与假手术组相比,气腹组大鼠肝组织细胞变性坏死严重,血清AST、ALT、肝组织IL-6、TNF-α及HMGB1、TLR4、MCP-1、ICAM-1、IFN-γ蛋白表达升高(P<0.05);与气腹组相比,丙泊酚各剂量组及阳性对照组大鼠肝组织细胞变性坏死缓解,血清AST、ALT、肝组织IL-6、TNF-α及HMGB1、TLR4、MCP-1、ICAM-1、IFN-γ蛋白表达降低(P<0.05),且丙泊酚剂量越高其改善效果越明显(P<0.05);丙泊酚高剂量组对肝损伤改善效果与阳性对照组相近(P>0.05)。结论:丙泊酚可抑制HMGB1/TLR4通路激活,降低肝组织炎症因子及趋化因子表达,缓解气腹大鼠肝脏损伤,改善肝功能。

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关键词 ：丙泊酚, 二氧化碳气腹, 肝功能, 高迁移率族蛋白B1/Toll样受体4通路

Abstract：Objective: To investigate the effects of propofol on liver function and high mobility group protein box 1 (HMGB1) / Toll-like receptor 4 (TLR4) pathway in with carbon dioxide pneumoperitoneum rats. Methods: The pneumoperitoneum model rats were established by setting the pneumoperitoneum pressure of 20 mmHg for 2 hours, the successful model rats were randomly divided into pneumoperitoneum group, propofol low (5mg/kg), medium (10mg/kg), high (20mg/kg) dose group and positive control group (biphenyl diester, 25mg/kg), with 10 rats in each group; and then a sham operation group (10 healthy rats) were constructed and operated by modeling without pneumoperitoneum. Two hours after operation, the sham operation group and pneumoperitoneum group were injected with normal saline intraperitoneally, propofol groups were injected intraperitoneally with propofol solution of corresponding dose, and the positive control group was given bifendate solution by gavage. Ten hours after the administration, the abdominal aortic blood and liver tissue were taken, and the liver function indexes serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), liver tissue inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) levels were detected by enzyme-linked immunosorbent assay. Hematoxylin eosin staining was used to detect the morphological changes of liver tissue. The protein expression of HMGB1, TLR4, monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and interferon-γ (IFN-γ) in liver tissue were detected by western blot.Results: Compared with those in sham operation group, the degeneration and necrosis of hepatocytes were serious in pneumoperitoneum group, the levels of serum AST, ALT, liver tissue IL-6, TNF-α, and the protein expression of HMGB1, TLR4, MCP-1, ICAM-1 and IFN-γ were higher (P<0.05). Compared with those in pneumoperitoneum group, the degeneration and necrosis of hepatocytes in the low, medium and high dose propofol groups and the positive control group were alleviated, the levels of serum AST, ALT, liver tissue IL-6, TNF-α, and the protein expression of HMGB1, TLR4, MCP-1, ICAM-1 and IFN-γ were lower (P<0.05), and the higher the dose of propofol, the more obvious the improvement effect (P<0.05); the improvement effect of propofol high dose group on liver injury was similar to that of positive control group (P>0.05).Conclusion: Propofol can inhibit the activation of HMGB1/TLR4 pathway, reduce the expression of inflammatory factors and chemokines in liver tissue, alleviate liver injury and improve liver function in rats with pneumoperitoneum.

Key words： Propofol Carbon dioxide pneumoperitoneum Liver function High mobility group protein box 1/Toll-like receptor 4 pathway

基金资助:湖北省卫生健康委员会科研项目,(编号:WJ2020M155)

通讯作者: 陈昊

引用本文:

艾玲, 徐卉, 陈昊. 丙泊酚对二氧化碳气腹大鼠肝功能及HMGB1/TLR4信号通路的影响[J]. 河北医学, 2022, 28(4): 539-543.
AI Ling, XU Hui, CHEN Hao. Effects of Propofol on Liver Function and HMGB1/TLR4 Signaling Pathway in with Carbon Dioxide Pneumoperitoneum Rats. HeBei Med, 2022, 28(4): 539-543.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2022.04.03 或 http://www.hbyxzzs.cn/CN/Y2022/V28/I4/539

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