天津医药

天津医药 ›› 2021, Vol. 49 ›› Issue (1): 28-31.doi: 10.11958/20201815

• 实验研究 • 上一篇    下一篇

柚皮油对心肺复苏后大鼠心肌坏死性凋亡的影响

赵高阳1，谢露2，王文艳1，邹鑫森1，田鑫悦1，陈蒙华1△   

  1. 1广西医科大学第二附属医院ICU（邮编530007）；2广西医科大学基础医学院生理学教研室
  • 收稿日期:2020-06-30 修回日期:2020-11-06 出版日期:2021-01-15 发布日期:2021-01-15
  • 通讯作者: 陈蒙华 E-mail:cmhnn@sina.com
  • 基金资助:
    ERK抑制剂经由线粒体动力学-自噬途径促进心肺复苏后神经细胞生存研究;ERK抑制剂调节心肺复苏后脑组织线粒体融合/分裂失衡，抑制神经细胞凋亡机制研究

Effects of pomelo peel oil on myocardial necroptosis in rats after cardiopulmonary resuscitation

ZHAO Gao-yang1, XIE Lu2, WANG Wen-yan1, ZOU Xin-sen1, TIAN Xin-yue1, CHEN Meng-hua1△   

  1. 1 The Intensive Care Unit of the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China; 
    2 Department of Physiology, School of Basic Medical Science, Guangxi Medical University
  • Received:2020-06-30 Revised:2020-11-06 Published:2021-01-15 Online:2021-01-15
  • Contact: MengHua Chen E-mail:cmhnn@sina.com
  • Supported by:
    heart arrest; cardiopulmonary resuscitation; myocardial reperfusion injury; tumor necrosis factor-alpha; MLKL; necroptosis; pomelo peel oil

PDF (PC)

963

摘要： 摘要：目的　探讨柚皮油对心肺复苏后大鼠心肌坏死性凋亡的影响。方法　将50只雄性SD大鼠按随机数字表法分为假手术组（Sham组）、模型组（CA组）、甘油组（GLY组）、低剂量柚皮油组（低剂量组）和高剂量柚皮油组（高剂量组），每组10只。Sham组仅行机械通气；其余4组均建立大鼠心脏骤停/心肺复苏（CA/CPR）模型，恢复自主循环（ROSC）后，静脉注射相应药物，CA组为生理盐水，GLY组为10%甘油，低剂量组为20 mg/kg柚皮油，高剂量组为40 mg/kg柚皮油。ROSC 24 h后，以HE染色和血清乳酸水平评价心肌损伤，免疫组化染色及蛋白免疫印迹法检测坏死性凋亡相关蛋白肿瘤坏死因子-α（TNF-α）和磷酸化混合谱系激酶结构域蛋白（p-MLKL）的表达。结果　HE染色显示CA组及GLY组心肌细胞肿胀、部分核固缩，低剂量组心肌细胞水肿、细胞破坏程度有所减轻，高剂量组心肌上述损伤明显减轻。CA组乳酸水平（mmol/L）较Sham组明显升高（1.50±0.11 vs. 0.91±0.10，P＜0.05），低剂量组（1.21±0.08）、高剂量组（1.07±0.09）较CA组及GLY组降低（P＜0.05），高剂量组较低剂量组降低（P＜0.05）。免疫组化染色及蛋白免疫印迹法检测结果显示，与Sham组比较，CA组及GLY组TNF-α和p-MLKL蛋白表达明显增高（P＜0.05）；与CA组比较，低剂量及高剂量组TNF-α和p-MLKL蛋白表达明显降低（P＜0.05）。CA组与GLY组各项指标相比差异无统计学意义。结论　柚皮油减轻心肺复苏后心肌缺血再灌注损伤的机制可能与抑制坏死性凋亡有关。

关键词: 心脏停搏, 心肺复苏术, 心肌再灌注损伤, 肿瘤坏死因子α, 混合谱系激酶结构域蛋白, 坏死性凋亡, 柚皮油

Abstract: Abstract: Objective　To explore the effect of pomelo peel oil on myocardial necroptosis in rats after cardiopulmonary resuscitation. Methods　According to the random number table method, 50 male SD rats were divided into the sham group (Sham group), model group (CA group), glycerol group (GLY group), low-dose pomelo oil group (Low-does group) and high-dose pomelo oil group (High-dose group), 10 rats in each group. The Sham group only performed surgery. The other 4 groups were all established rat cardiac arrest/cardiopulmonary resuscitation (CA/CPR) models. After resumption of spontaneous circulation (ROSC), drugs were injected intravenously into CA group (normal saline), GLY group (10% glycerol), Low-dose group (20 mg/kg pomelo peel oil) and High-dose group (40 mg/kg pomelo peel oil). The lactic acid level and myocardial tissue HE staining were used for evaluating myocardial injury. Immunohistochemistry and Western blot assay were adopted for detecting TNF-α and p-MLKL in each group at 24 hours after resuscitation. Results　HE staining found that myocardial fiber swelling and nuclear contraction were serious in CA and GLY groups, myocardial cell swelling and cell destruction degree were slightly reduced in Low-dose group, and myocardial injury was significantly reduced in High-dose group. The lactic acid level (1.50 mmol/L±0.11 mmol/L) was significantly higher in the CA group than that in the Sham group (0.91 mmol/L±0.10 mmol/L) (P＜0.05). The lactic acid levels were significantly lower in the Low-dose group and High-dose group (1.21 mmol/L±0.08 mmol/L and 1.07 mmol/L±0.09 mmol/L) than those in CA and GLY groups (P＜0.05). The lactic acid levels were significantly lower in High-dose group than those in Low-dose group (P＜0.05). Immunohistochemistry and Western blot assay showed that compared with the Sham group, the expression levels of TNF-α and p-MLKL were significantly increased in CA group and GLY group (P＜0.05). Compared with CA group, the expressions of TNF-α and p-MLKL decreased significantly in Low-dose group and High-dose group (P＜0.05). There was no statistically significant difference in all indicators between the CA group and the GLY group. Conclusion　Pomelo peel oil may reduce myocardial ischemia-reperfusion injury by inhibiting necroptosis.