丹参酮ⅡA对内毒素血症小鼠心肌损伤的预防作用及机制  

Preventive effect and mechanism of tanshinoneⅡA on myocardial injury in endotoxemia mice

作　　者：陶静[1] 王元元[1] 马善峰[2] 李言[3] 倪虹[1] 丁海虎[1] 赵继利 王锐[4] 张甫 陶明飞[1] TAO Jing(Functional Comprehensive Laboratory of Bengbu Medical College,Bengbu 233030,China)

机构地区：[1]蚌埠医学院机能综合实验室,安徽蚌埠233030 [2]蚌埠医学院生理教研室,安徽蚌埠233030 [3]蚌埠医学院病理生理教研室,安徽蚌埠233030 [4]蚌埠医学院科研中心,安徽蚌埠233030 [5]固镇县人民医院心血管科,安徽蚌埠233700

出　　处：《牡丹江医学院学报》2020年第2期6-9,37,共5页Journal of Mudanjiang Medical University

基　　金：安徽省蚌埠医学院自然科学基金(BYKY1656;BYKY1647)。

摘　　要：目的观察脂多糖诱导小鼠内毒素血症发生时的心肌损伤情况,及丹参酮ⅡA(TⅡA)对心肌损伤有无预防保护作用,是否与RhoA/Rock(Rho激酶)通路激活有关。方法雄性8~10周龄C57BL/6J小鼠40只,SPF级,体重(20±2)g,依据随机数字表法将小鼠随机分成空白对照组(CON组)、模型组(LPS组)、丹参酮预处理组(TL组)以及丹参酮组(T组)(n=10)。利用腹腔注射脂多糖(LPS)建立内毒素血症模型。TL组和T组,注射丹参酮10mg/(kg·d)共7d;CON组,LPS组生理盐水等体积注射7d。LPS组、TL组末次注射1h后,腹腔注射LPS(10mg/kg)。LPS注射6h后,超声心动图测定小鼠心功能。12h后,心肌组织做HE染色,光镜下观察小鼠心肌形态结构的变化;酶联免疫吸附实验,检测心肌组织白介素-1β(IL-1β)的蛋白水平;蛋白质印迹法(Western blot)检测小鼠心肌组织RhoA和Rock1的蛋白含量。结果超声心动图结果表明,与CON组比,LPS组和TL组,心率(HR)、射血分数(EF)、短轴缩短率(FS)、每搏输出量(SV)和心输出量(CO)均下降(P<0.05),与LPS组相比,TL组HR、SV、EF、FS和CO均升高(P<0.05);HE染色显示,LPS组心肌组织横纹模糊,胞浆淡染,有炎细胞浸润,TL组未见心肌组织形态学明显改变;与CON组相比,LPS组心肌组织IL-1β、RhoA和Rock1蛋白含量均升高(P<0.05),与LPS组相比,TL组可以降低IL-1β、RhoA和Rock1蛋白含量(P<0.05)。结论内毒素血症引起的小鼠心肌损伤,在丹参酮ⅡA预处理下,可以降低炎性因子,减轻损伤,其作用可能与抑制RhoA/Rock(Rho激酶)通路激活有关。Objective To observe the myocardial damage caused by endotoxemia which was induced by lipopolysaccharide in mice,and to investigate whether TanshinoneⅡA(TⅡA)has a preventive and protective effect on myocardial damage,which may be related to the activation of RhoA/Rock(Rho kinase)pathway.Methods Forty male C57BL/6J mice aged 8~10w,SPF grade,body weight(20±2)g,were randomly divided into blank control group(CON group),model group(LPS group),tanshinone pretreatment according to random number table method Group(TL group)and tanshinone group(T group)(n=10).Endotoxemia model was established by intraperitoneal injection of lipopolysaccharide(LPS).In the TL group and T group,10 mg/(kg·d)of tanshinone was injected for 7 days.In the CON group and LPS group,normal saline was injected for 7 days.LPS group and TL group were injected intraperitoneally with LPS(10mg/kg)1h after the last injection.Six hours after LPS injection,echocardiography was used to determine the cardiac function of mice.After 12h,myocardial tissues were stained with HE,and the changes of morphology and structure of mouse myocardium were observed under light microscope.Enzyme-linked immunosorbent assay was used to detect the protein level of interleukin-1β(IL-1β)in cardiac muscle tissue.The protein content of RhoA and Rock1 in mouse myocardium were detected by Western blot.Results Compared with CON group,echocardiographic results showed that heart rate(HR),ejection fraction(EF),short axis shortening rate(FS),stroke volume(SV)and cardiac output(CO)in LPS group and TL group were decreased(P<0.05).Compared with the LPS group,HR,SV,EF,FS and CO were increased in the TL group(P<0.05).HE staining showed that the myocardial tissue of the LPS group had blurred stripes,pale cytoplasm staining,and infiltration of inflammatory cells.There were no significant changes in myocardial tissue morphology in the TL group.Compared with the CON group,IL-1β,RhoA and Rock1 protein content in myocardial tissue of the LPS group were increased(P<0.05).Compared with the LPS

关 键 词：脂多糖 丹参酮 心肌损伤 炎症因子 RhoA/Rock 

分 类 号：R331[医药卫生—人体生理学]