丹酚酸B预处理对缺血/再灌注损伤的保护机制研究  

Cardioprotective Mechanisms of Salvianolic Acid B Pretreatment against Myocardial Ischemia/Reperfusion Injury

作　　者：夏杨[1] 张惠军[1] 李强[1] XIA Yang;ZHANG Huijun;LI Qiang(Fourth Department of Internal Medicine,Beijing Armed Police Forces Hospital,Beijing 100027,China)

机构地区：[1]武警北京总队医院内四科,北京100027

出　　处：《中国药物警戒》2018年第11期644-647,667,共5页Chinese Journal of Pharmacovigilance

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 adhesionmolecule-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。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 into4groups(n=20):sham,model,Sal B low dose(10mg·kg^-1)and Sal B high dose(20mg·kg^-1).Before the modeling operation,Sal B was injected intraperitoneally once daily for7days.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(20and10mg·kg^-1)were reduced to35.93%and37.21%,respectively(P<0.05).Comparing with model group(337.84U·g^-1),myocardial MPO activities in Sal B groups(20 and 10mg·kg^-1)were 201.63 and 213.77U·g^-1,respectively(P<0.01).Comparing with model group(71.06%),positive area percentages of myocardial ICAM-1expression in Sal B groups(20and10mg·kg^-1)were 36.37% and 36.94%,respectively(P<0.01).Comparing with model group(238.21pg·mL^-1),myocardial TNF-αlevels in Sal B groups(20and10mg·kg^-1)were162.18and181.57pg·mL^-1,respectively(P<0.01).Comparing with model group(607.41pg·mL^-1),myocardial IL-1βlevels in Sal B groups(20 and 10mg·kg^-1)were 395.13 and 399.04pg·mL^-1respectively(P<0.05or 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.

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 

分 类 号：R965[医药卫生—药理学]