天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (8): 794-799.doi: 10.11958/20190284

• 实验研究 • 上一篇    下一篇

水飞蓟宾对内毒素血症心肌损伤的保护作用及机制

陈旭1，王晓武2，江丽青2，马继鹏2，冯建宇2△   

  1. 1 深圳市人民医院心脏大血管外科（邮编518000）；2 空军军医大学西京医院心血管外科
  • 收稿日期:2019-01-28 修回日期:2019-04-21 出版日期:2019-08-15 发布日期:2019-08-16
  • 通讯作者: 冯建宇 E-mail:351446914@qq.com
  • 作者简介:陈旭（1985），男，硕士，主治医师，主要从事心肌保护策略机制方面研究
  • 基金资助:
    国家自然科学基金

The protective effect and mechanism of silibinin on cardiac injury induced by endotoxemia

CHEN Xu1, WANG Xiao-wu2, JIANG Li-qing2, MA Ji-peng2, FENG Jian-yu2△   

  1. 1 Department of Cardiovascular Surgery, Shenzhen People’s Hospital, Shenzhen 518000, China; 2 Department of Cardiovascular Surgery, Xijing Hospital, Air Force Military Medical University
  • Received:2019-01-28 Revised:2019-04-21 Published:2019-08-15 Online:2019-08-16

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摘要： 摘要：目的探究水飞蓟宾（SIL）对小鼠内毒素血症心肌损伤的保护作用和分子机制。方法24只C57BL/6小鼠分为对照（Control）组、SIL组、LPS组、LPS+SIL组，每组6只。通过腹腔注射脂多糖（LPS，10 mg/kg）制备内毒素血症心肌损伤小鼠模型。LPS注射前3 d，SIL组和LPS+SIL组每日通过灌胃方式给予SIL（100 mg/kg），共给药3次；Control组和LPS组每日通过灌胃方式给予等量（0.2 mL）生理盐水，共灌胃3次。LPS注射6 h后超声检测各组小鼠心脏收缩功能；ELISA检测血清IL-1β和TNF-α表达水平；DHE染色观察各组小鼠心肌组织内活性氧（ROS）产量；TUNEL染色检测心肌凋亡率；Western blot检测凋亡相关蛋白Bax、Bcl-2、Caspase 3和NOX2表达。结果与Control组相比，LPS组小鼠左心室射血分数、左心室短轴缩短率和Bcl-2表达量明显降低，而ROS产量、NOX2、Bax、Caspase 3、IL-1β与TNF-α表达量以及心肌凋亡率明显增加（P＜0.05）。与LPS组相比，LPS+SIL组经水飞蓟宾预处理后可明显改善LPS引起的上述改变（P＜0.05）。与Control组相比，单纯给予SIL干预对上述指标的变化无明显影响（P＞0.05）。结论水飞蓟宾可有效缓解内毒素血症心肌损伤，其作用可能与抑制氧化应激、炎症反应和抗凋亡有关。

关键词: 内毒素血症, 脂多糖类, 心肌收缩, 细胞凋亡, 活性氧, 炎症, 水飞蓟宾

Abstract: Abstract: Objective To explore the protective effect and molecular mechanism of silibinin (SIL) on myocardial injuryin endotoxemic mice. Methods Twenty-four C57BL/6 mice were grouped as follows: Control group, SIL group, LPS group and LPS + SIL group (n=6 in each group). The mouse model of endotoxemic cardiomyopathy was established by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg). Three days before LPS injection, SIL was administered daily by gavage at a dose of 100 mg/kg for 3 times in the SIL group and the LPS+SIL group. The mice in the Control group and the SIL group were treated with normal saline (0.2 mL, by gavage) for 3 times. Six hours after LPS injection, the cardiac contractile function was detected by ultrasound in mice, the expression levels of serum IL-1β and TNF-α were detected by ELISA, the production of reactive oxygen species (ROS) in heart tissue was observed by DHE staining, the apoptotic ratio was detected by TUNEL staining and the expression of apoptosis-related proteins (Bax, Bcl-2, Caspase 3) and NOX2 were detected by Western blot assay. Results Compared with the Control group, the left ventricular ejection fraction, left ventricular fractional shortening and Bcl-2 expression were significantly decreased, while ROS production, the expressions of NOX2, Bax, Caspase 3, IL-1β, TNF-α and the apoptotic ratio were significantly increased in the LPS group (P＜0.05).Compared with the LPS group, silibinin pretreatment significantly improved the above changes caused by LPS (P＜0.05).Compared with the Control group, SIL alone showed little influence on the parameters metioned above (P＞0.05).Conclusion Silibinin can effectively alleviate myocardial injury in endotoxemic mice, and its cardioprotective role is possibly mediated by inhibiting oxidative stress, inflammatory response and apoptosis.

Key words: endotoxemia, lipopolysaccharides, myocardial contraction, apoptosis, reactive oxygen species, inflammation, silibinin