丹酚酸B预处理对缺血/再灌注损伤的保护机制研究

摘要/Abstract

摘要： 目的研究丹酚酸B预处理对心肌缺血/再灌注损伤（myocardial ischemia/reperfusion injury, MI/RI）的保护作用及机制。方法通过结扎冠脉30 min再灌注2 h的方式制备大鼠MI/RI模型,随机分为4组：假手术组、模型组、丹酚酸B高剂量组（20 mg·kg-1）、丹酚酸B低剂量组（10 mg·kg-1）,于制备模型前7 d开始腹腔注射给药;再灌注结束后,采用染色法检测心肌梗死面积（myocardial infarction area, MIA）,比色法检测心肌组织髓过氧化物酶（myeloperoxidase, MPO）活力,酶联免疫吸附法检测心肌组织肿瘤坏死因子-α（tumor necrosis factor-α, TNF-α）和白介素-1β（interleukin-1β, IL-1β）的表达水平,免疫组化法检测心肌组织细胞间黏附分子-1（intercellular cell adhesion molecule-1, ICAM-1）的阳性表达。结果与模型组（42.60%）相比,丹酚酸B高、低剂量组的MIA分别缩小至35.93%和37.21%（P <0.05）;与模型组（337.84 U·g-1）相比,丹酚酸B高、低剂量组心肌MPO活力分别为201.63、213.77 U·g-1（P <0.01）;与模型组（71.06%）相比,丹酚酸B高、低剂量组心肌ICAM-1的阳性区面积百分比分别为36.37%和36.94%（P <0.01）;与模型组（238.21 pg·mL-1）相比,丹酚酸B高、低剂量组心肌TNF-α水平分别为162.18、181.57 pg·mL-1（P <0.01）;与模型组（607.41 pg·mL-1）相比,丹酚酸B高、低剂量组心肌IL-1β水平分别为395.13、399.04 pg·mL-1（P < 0.05或P <0.01）。结论丹酚酸B预处理可保护MI/RI的受损心肌,机制可能与抑制黏附分子、减少中性粒细胞浸润、下调炎性细胞因子、改善心肌组织的炎症反应相关。

关键词: 丹酚酸B, 心肌缺血/再灌注损伤, 大鼠, 炎症反应, 黏附分子

Abstract: Objective To investigate the effects of salvianolic acid B (Sal B) on rats with myocardial ischemia/reperfusion injury (MI/RI) and its mechanisms involved. Methods MI/RI model in SD rats was prepared by 30 min of coronary artery ligation and subsequent 2 hours of reperfusion. Rats were randomized into 4 groups (n=20): sham, model, Sal B low dose (10 mg·kg-1) and Sal B high dose (20 mg·kg-1). Before the modeling operation, Sal B was injected intraperitoneally once daily for 7 days. After the reperfusion, myocardial infarction area (MIA) in rats was examined by staining method, myeloperoxidase (MPO) activity in myocardial tissue was detected by chromatometry, levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in myocardial tissue were determined by ELISA and expression of intercellular cell adhesion molecule-1 (ICAM-1) in myocardial tissue was examined by immunohistochemistry. Results Comparing with model group (42.60%), MIAs in Sal B groups (20 and 10 mg·kg-1) were reduced to 35.93% and 37.21%, respectively (P <0.05). Comparing with model group (337.84 U·g-1), myocardial MPO activities in Sal B groups (20 and 10 mg·kg-1) were 201.63 and 213.77 U·g-1, respectively (P <0.01). Comparing with model group (71.06%), positive area percentages of myocardial ICAM-1 expression in Sal B groups (20 and 10 mg·kg-1) were 36.37% and 36.94%, respectively (P <0.01). Comparing with model group (238.21 pg·mL-1), myocardial TNF-α levels in Sal B groups (20 and 10 mg·kg-1) were 162.18 and 181.57 pg·mL-1, respectively (P <0.01). Comparing with model group (607.41 pg·mL-1), myocardial IL-1β levels in Sal B groups (20 and 10 mg·kg-1) were 395.13 and 399.04 pg·mL-1, respectively (P <0.05 or P <0.01). Conclusion Sal B pretreatment could protect MI/RI, its mechanisms may be related with inhibition of intercellular cell adhesion molecule expression and neutrophil infiltration, downregulation of inflammatory cytokines and improvement of inflammation.

Key words: salvianolic acid B, myocardial ischemia/reperfusion injury, rat, inflammation, adhesion molecule

中图分类号:

R965

夏杨, 张惠军, 李强. 丹酚酸B预处理对缺血/再灌注损伤的保护机制研究[J]. 中国药物警戒, 2018, 15(11): 644-647.

XIA Yang, ZHANG Huijun, LI Qiang. Cardioprotective Mechanisms of Salvianolic Acid B Pretreatment against Myocardial Ischemia/Reperfusion Injury[J]. Chinese Journal of Pharmacovigilance, 2018, 15(11): 644-647.

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