丁苯酞和TLR4抑制剂预处理对冠状动脉微栓塞大鼠心肌损伤的改善作用及其机制  

Effect of butylphthalide combined with TTLR4 pretreatment on myocardial injury of rats with coronary microembolization and its mechanism

作　　者：黄骏文 陈志清 周游[1] 李浪[1] HUANG Junwen;CHEN Zhiqing;ZHOU You;LI Lang(Cardiovascular Medicine Department,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;不详)

机构地区：[1]广西医科大学第一附属医院心血管内科,南宁530021 [2]前海人寿南宁医院心血管内科

出　　处：《山东医药》2022年第3期39-43,共5页Shandong Medical Journal

摘　　要：目的 探讨丁苯酞(NBP)联合Toll样受体4(TLR4)抑制剂预处理对冠状动脉微栓塞大鼠心肌损伤的改善作用及机制。方法 将32只SD大鼠按随机数字表法分为NBP+TAK-242组、NBP组、CME组、Sham组,每组8只。NBP+TAK-242组CME术前予NBP 80 mg/kg连续灌胃7 d,CME术前30 min按2 mg/kg尾静脉注射0.5 mg/mL的TLR4抑制剂TAK-242;NBP组CME术前予NBP 80 mg/kg连续灌胃7 d;其余各组同法注射4 mL/kg的生理盐水。然后,NBP+TAK-242组、NBP组、CME组左心室注入直径42μm微栓塞球混悬液0.1 mL,Sham组注射0.1 mL生理盐水。CME术后6 h,检测各组大鼠心功能指标,苏木精—伊红染色(HE)及苏木精—碱性品红苦味酸染色(HBFP)观察心肌组织病理改变;RT-PCR检测心肌组织TLR4 mRNA,Western blotting法检测心肌组织TLR4通路相关蛋白(TLR4、myD88、NF-κB)及炎性因子(IL-1β、TNF-α蛋白)。结果 与Sham组相比,CME组大鼠心功能射血分数(LVEF)和短轴缩短率(FS)降低(P均<0.01),左心室收缩末期内径(LVEDs)增加(P<0.01);HE染色可见明显白细胞浸润,心肌微梗死面积增加(P<0.01);心肌TLR4 mRNA相对表达量升高(P<0.01);心肌TLR4通路相关蛋白及炎性因子相对表达量升高(P均<0.05)。与CME组相比,NBP组及NBP+TAK-242组LVEF、FS升高(P均<0.01),左心室舒张末期内径(LVEDd)、LVEDs降低(P均<0.01);心肌炎性细胞浸润减少,心肌微梗死面积减少(P均<0.01);TLR4 mRNA相对表达量降低(P<0.01);心肌TLR4通路相关蛋白及炎性因子相对表达量均降低(P均<0.05)。与NBP组相比,NBP+TAK-242组LVEF、FS升高(P<0.05);心肌炎性细胞浸润较少,心肌微梗死面积减少(P<0.01);心肌TLR4、MyD88、IL-1β、TNF-α蛋白相对表达量进一步降低(P均<0.05)。结论 NBP和TLR4抑制剂预处理可改善冠状动脉微栓塞大鼠的心肌损伤,预处理效果优于单用NBP,其作用机制可能与抑制LR4/myD88/NF-κB信号通路及炎性因子有关。Objective pretreatment on myocarditis after coronary microembolization(CME)in rats and its mechanism.Methods SD rats were randomly divided into the CME group,sham operation group(Sham group),CME+NBP group,and butylphthalide+TLR4 inhibitor group(NBP+TAK-242 group),with 8 in each. CME models were produced by injection of42 μm microspheres into the left ventricle,while the rats in the Sham group were injected with saline(0. 1 mL)instead.Rats in the NBP group were given NBP 80 mg/kg for 7 days before operation. In the NBP+TAK-242 group,TAK-242 mg/kg was injected at 30 min before operation on the basis of treatment of the NBP group. While the same volume of saline was injected into rats of the other groups. Six hours after operation,the cardiac function of rats in each group was measured,the pathological changes of myocardial tissues were observed by HE and HBFP staining,the relative expression level of TLR4 mRNA in the myocardial tissues was detected by RT-PCR,and the protein relative expression levels of TLR4,myD88,NF-κB,IL-1β and TNF-α were detected by Western blotting.Results the left ventricular ejection fraction(EF)and left ventricular fractional shortening(FS)decreased significantly in the CME Group(both P<0. 01),while left ventricular end-systolic diameter(LVEDs)increased significantly(P<0. 01);the inflammatory cell infiltration was observed in the myocardial tissues by HE staining,myocardial micro infarction was observed by HBFP staining,the relative expression level of TLR4 mRNA increased significantly(P<0. 01);the relative expression levels of TLR4 pathway-related proteins and inflammatory factors increased significantly(all P<0. 05). Compared with the CME Group,LVEF and FS of the NBP group and NBP + TAK-242 group increased significantly(all P<0. 01),while the left ventricular end-diastolic diameter(LVEDd)and LVEDs decreased significantly(all P<0. 01),inflammatory cell infiltration and infarction area decreased significantly(both P<0. 01),the relative expression level of TLR4 mRNA decreased significantl

关 键 词：丁苯酞 Toll样受体4抑制剂 冠状动脉微栓塞 心肌损伤 炎症反应 

分 类 号：R541.4[医药卫生—心血管疾病]