摘要
目的探究大黄素通过调控miR-16-5p/信号转导和转录激活因子3(STAT3)对心肌梗死大鼠模型发挥保护作用的机制。方法取Wistar大鼠随机分为假手术组、模型组、大黄素低剂量组、大黄素高剂量组、miR-16-5p agomir组、miR-16-5p agomir阴性对照组、大黄素高剂量+miR-16-5p agomir组,每组12只。模型组和实验处理组大鼠通过冠状动脉左前降支结扎法建立心肌梗死模型,假手术组大鼠仅穿线不结扎,分组处理后,测定7组大鼠心功能指标左心室收缩末期内径(LVDS)、左心室舒张末期内径(LVDD)、左心室射血分数(EF);以TTC染色检测7组大鼠心肌梗死面积;以HE和TUNEL染色分别检测7组大鼠心肌组织病理变化及心肌细胞凋亡率;以酶联免疫吸附(ELISA)法测定7组大鼠血清及心肌组织炎性因子IL-1β、TNF-α水平;以实时荧光PCR检测7组大鼠心肌组织miR-16-5p水平;以免疫印迹法检测7组大鼠心肌组织凋亡蛋白(Bax、Caspase-3)及STAT3表达。结果与假手术组比较,模型组大鼠心肌组织呈现严重病理损伤,LVDS、LVDD、心肌梗死面积、心肌细胞凋亡率、血清及心肌组织IL-1β、TNF-α水平、心肌组织Bax、Caspase-3蛋白表达、miR-16-5p表达及p-STAT3/STAT3明显升高(P<0.05),EF明显降低(P<0.05)。与模型组比较,大黄素低、高剂量组大鼠心肌组织病理损伤均减轻,LVDS、LVDD、心肌梗死面积、心肌细胞凋亡率、血清及心肌组织IL-1β、TNF-α水平、心肌组织Bax、Caspase-3蛋白表达、miR-16-5p表达及p-STAT3/STAT3均降低(P<0.05),EF均升高(P<0.05);大黄素高剂量组大鼠心肌组织病理损伤比大黄素低剂量组进一步减轻,LVDS、LVDD、心肌梗死面积、心肌细胞凋亡率、血清及心肌组织IL-1β、TNF-α水平、心肌组织Bax、Caspase-3蛋白表达、miR-16-5p表达及p-STAT3/STAT3进一步降低(P<0.05),EF进一步升高(P<0.05);miR-16-5p agomir组大鼠心肌组织病理损伤加重,LVDS、LVDD、心肌梗死面积、心�
Objective To explore the protective mechanism of emodin on myocardial infarction in rats by regulating the miR-16-5p/signal transducer and activator of transcription 3(STAT3)axis.Methods Wistar rats were randomly divided into sham operation group,model group,low-dose emodin group,high-dose emodin group,miR-16-5p agomir group,miR-16-5p agomir negative control group,and high-dose emodin+miR-16-5p agomir group,with 12 rats in each group.Myocardial infarction modeling by ligating the left anterior descending coronary artery was performed in rats of all groups,except for those in sham operation group who were only treated with suture treading.After grouping and treatment,the left ventricular end systolic diameter(LVDS),left ventricular end diastolic diameter(LVDD)and left ventricular ejection fraction(EF)were measured.triphenyltetrazolium chloride(TTC)staining was used to detect the myocardial infarction area of rats in each group.hematoxylin and eosin(H&E)staining and transferase dUTP nick end labeling(TUNEL)assay were used to detect the pathological changes of myocardium and the apoptosis rate of myocardial cells,respectively.Relative levels of inflammatory factors,including IL-1βand TNF-αin serum and myocardium of rats in each group were measured by enzyme-linked immunosorbent assay(ELISA).Relative level of miR-16-5p in rat myocardial tissues was detected by real-time fluorescent PCR.The protein expressions of apoptosis proteins(Bax,Caspase-3)and STAT3 in rat myocardial tissues were detected by Western blot.Results Compared with those of the sham operation group,rats in model group showed obvious myocardial damages,significantly enlarged myocardial infarct area,significantly increased LVDS,LVDD,apoptotic rate of myocardial cells,relative levels of IL-1βand TNF-αin serum and myocardium,expression levels of Bax,Caspase-3,miR-16-5p and p-STAT3/STAT3,and significantly decreased EF(P<0.05).The above pathological changes were significantly reversed by emodin treatment,especially the treatment of high-dose emodin.Howe
作者
谢小芳
赵展庆
符妹垂
XIE Xiaofang;ZHAO Zhanqing;FU Meichui(Department of Critical Care Medicine,Hainan Western Central Hospital,Hainan,Danzhou 571700,China;不详)
出处
《河北医药》
CAS
2023年第11期1605-1610,共6页
Hebei Medical Journal
基金
海南省自然科学基金项目(编号:820MS154)。
