丹参注射液抑制炎症和氧化应激水平保护脓毒症大鼠免受心肌损伤  

Danshen injection protects sepsis rats from myocardial injury by inhibiting inflammation and oxidative stress

作　　者：罗晓梅[1] 吴玉珠[1] 黄培渝 张淑芬[1] 赖小琴 LUO Xiaomei;WU Yuzhu;HUANG Peiyu;ZHANG Shufen;LAI Xiaoqin(Department of Pharmacy,Second Affiliated Hospital of Fujian Medical University,Quanzhou 362000,China)

机构地区：[1]福建医科大学附属第二医院药学部,泉州362000

出　　处：《免疫学杂志》2020年第7期585-591,共7页Immunological Journal

基　　金：福建省自然科学基金(2016J01432)。

摘　　要：目的探讨丹参注射液(Danshen injection,DSI)对脓毒症大鼠心肌损伤的保护作用及其机制。方法采用盲肠结扎穿孔法复制脓毒症大鼠模型。大鼠分成6组:对照组(Control组)、模型组(Model组)、DSI低中高剂量组(1、2、4 ml/kg)和阳性对照组。检测大鼠血液动力学参数;HE和TUNEL染色观察心肌损伤;ELISA检测炎症和氧化应激指标含量;免疫组化检测心肌组织中增殖蛋白表达;蛋白印迹法检测心肌组织中凋亡、增殖及通路蛋白表达水平。结果与模型组相比,丹参注射液改善脓毒症大鼠心肌损伤,增加平均动脉压、心率和左室收缩压,降低心肌细胞凋亡和cl-caspase-3、cl-caspase-9、Bax表达,增加Bcl-2表达,增加心肌组织Ki67和PCNA表达,抑制TNF-α、IL-6和IL-1β产生,增加抗氧化酶SOD含量,降低氧化产物MDA含量,还增加抗氧化酶Nrf2、HO-1和NQO1表达,下调炎症通路蛋白TLR4和P-P65。结论丹参注射液可能通过Nrf2和TLR4信号通路抑制脓毒症大鼠心肌损伤。This study was designed to investigate the protective effect of Danshen injection(DSI)on myocardial injury in sepsis rats and its mechanism.The sepsis rat model was established by cecal ligation and perforation.Rats were divided into 6 groups:control group,model group,DSI groups(1,2,4 ml/kg),and positive control group.Hemodynamic parameters of all rats were measured.HE and TUNEL staining were used to observe myocardial injury;ELISA was used to detect the content of inflammatory and oxidative stress indicators;immunohistochemistry was used to detect the expression of proliferative protein in myocardial tissue;Western blotting was used to detect the expression of apoptosis,proliferation and pathway proteins in myocardial tissue.Date showed that DSI improved myocardial injury,increased the levels of mean ventricular systolic pressure,heart rate and left ventricular systolic pressure,decreased myocardial cell apoptosis and the expression of cl-caspase-3,cl-caspase-9 and Bax.Furthermore,DSI also increased the expression of Bcl-2,Ki67 and PCNA in myocardial tissue,while inhibited the production of TNF-alpha,IL-6 and IL-1β;DSI increased the content of SOD but decrease MDA,increased the expression of antioxidant enzymes Nrf2,HO-1 and NQO1,while down-regulated inflammatory pathway proteins TLR4 and P-P65.In conclusion,DSI could inhibit myocardial injury in sepsis rats through Nrf2 and TLR4 signaling pathways.

关 键 词：丹参注射液 转录因子NF-E2相关因子 血红素氧合酶-1 醌氧化还原酶1 TOLL样受体4 

分 类 号：R285.5[医药卫生—中药学]