机构地区:[1]中国医学科学院北京协和医学院国家心血管病中心阜外医院心血管疾病国家重点实验室,北京100037
出 处:《中西医结合心脑血管病杂志》2017年第6期671-676,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基 金:北京中医药薪火传承3+3工程专项
摘 要:目的评价长期应用不同剂量红景天苷对于急性心肌梗死大鼠心室重构方面相关作用及机制。方法建立结扎SD大鼠左前降支冠脉造急性心梗的模型,随机分为6组:红景天苷低、中、高剂量组(MI+SALL、MI+SALM、MI+SALH),卡维地洛对照组(MI+CAVE),模型组(MI),假手术组(Sham)。灌胃给药干预56 d后超声评价监测心功能变化,计算左心室重量指数(LVW/BW)和全心重量指数(HW/BW),测量左室射血分数(LVEF)、左室缩短率(LVFS)、左心室收缩期内径(LVIDS)。取梗死周边心肌组织,利用HE染色,Masson染色,天狼星红染色分别观察心肌组织病理生理学改变及心肌纤维化面积、非梗死区Ⅰ/Ⅲ型胶原比值。利用Western blot分析检测Wnt/β-catenin信号通路关键的信号分子DVL-1和β-catenin蛋白的表达,整理数据统计分析。结果与Sham组比较,MI组LVEF、LVFS值明显下降(P<0.01),LVIDS上升、HW/BW值较高(P<0.05),LVW/BW值则处于低水平(P<0.01);灌胃后各组大鼠心肌梗死区域室壁总体变薄。HE染色结果显示,左室病理生理学改变显著;Masson染色结果显示,梗死周边区心肌胶原纤维明显增多,纤维瘢痕形成,心肌胶原面积较大;天狼星红染色结果显示有明显Ⅰ型、Ⅲ型胶原的沉积;梗死周边区Wnt/β-catenin Pathway中的关键性信号蛋白DVL-1和β-catenin呈现高表达水平(P<0.05)。与MI组比较,各治疗组可见有炎性细胞浸润,纤维组织增生,肌原纤维溶解;其中MI+SALM组LVEF和LVFS、LVW/BW值上升,Ⅰ/Ⅲ型胶原比值下降(P<0.05),MI+SALL组和MI+CAVE组心肌胶原面积、Ⅰ/Ⅲ型胶原比值明显下调(P<0.01),LVEF和LVFS、LVW/BW值明显升高(P<0.01),DVL-1和β-catenin的表达水平均明显下降(P<0.05或P<0.01)。两组之间无统计学意义(P>0.05)。MI+SALH组心肌胶原面积有一定程度减小(P<0.05)。各组体重变化及HW/BW值均无统计学意义(P>0.05)。结论长期治疗干预下,应用小剂量的红景天苷优于中高剂量,能显著�Objective To investigate the effect and mechanism of salidroside on ventricular remodeling after acute myocardial infarction(AMI)in rats.Methods The AMI rat model was established by ligating the left anterior descending coronary artery.The Sprague-Dawley(SD)rats were randomly divided into 7 groups:sham operation group,model group,carvedilol control group,low-,middle-and high-dose salidroside group.After 56 days of administration,the left ventricular mass index(LVW/BW)and total heart weight index(HW/BW)were calculated and the left ventricular ejection fraction(LVEF)and left ventricular shortening rate(LVW)were measured.The left ventricular fractional shortening(LVFS)and left ventricular systolic diameter(LVIDS)in the infarcted myocardium were measured by HE staining,Masson staining and Sirius red staining.The ratio of type Ⅰ/Ⅲ collagen in the non-infarcted area was measured by the histopathological changes and myocardial fibrotic area The expressions of disheveled-1(DVL-1),β-catenin,a key signal of Wnt/β-catenin signaling pathway,were detected by Western blot analysis.The data was analyzed statistically.Results Compared with sham operation group,the myocardial pathological changes were significantly higher in model group(P 〈0.05).The myocardial collagen fibers in the infarcted area were significantly increased in model group(P 〈0.01).LVIDs increased and HW/BW was higher in model group(P 〈0.01),and the collagenous area of cardiac muscle was larger in model group(P 〈0.01).The results of Sirius red staining showed that collagenⅠ,Ⅲ collagen deposition,LVEF and LVFS were significantly decreased in model group(P 〈0.01).The expression of DVL-1 andβ-catenin in infarcted area was significantly higher in model group(P 〈0.05).Compared with model group,inflammatory cell infiltration,fibrous tissue hyperplasia and myofibrillysis were found in each treatment group.LVEF and LVFS and LVW/BW increased,and collagen typeⅠ/Ⅲ decreased in middle-d
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