PDF(Pubmed)
Abstract：
OBJECTIVE: Exploring the effect of Optimized New Shengmai powder (, ONSMP) on myocardial fibrosis in heart failure (HF) based on rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinases (ERK) signaling pathway.
METHODS: Randomized 70 Sprague-Dawley rats into sham (n = 10) and operation (n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low (L), medium (M), and high (H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat\'s body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen (COL) I and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the mRNA levels of COL I, COL Ⅲ, α-smooth muscle actin (α-SMA), and c-Fos proto-oncogene (c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor (p-ELK1), p-c-Fos, α-SMA, COL I, and COL Ⅲ by Western blot.
RESULTS: ONSMP can effectively improve HF rat\'s cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL I/Ⅲ content, down-regulate the mRNA of COL I/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/ 2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA.
CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.
METHODS: Randomized 70 Sprague-Dawley rats into sham (n = 10) and operation (n = 60) groups, then established the HF rat by ligating the left anterior descending branch of the coronary artery. We randomly divided the operation group rats into the model, ONSMP [including low (L), medium (M), and high (H) dose], and enalapril groups. After the 4-week drug intervention, echocardiography examines the cardiac function and calculates the ratios of the whole/left heart to the rat\'s body weight. Finally, we observed the degree of myocardial fibrosis by pathological sections, determined myocardium collagen (COL) I and COL Ⅲ content by enzyme-linked immunosorbent assay, detected the mRNA levels of COL I, COL Ⅲ, α-smooth muscle actin (α-SMA), and c-Fos proto-oncogene (c-Fos) by universal real-time, and detected the protein expression of p-RAS, p-RAF, p-MEK1/2, p-ERK1/2, p-ETS-like-1 transcription factor (p-ELK1), p-c-Fos, α-SMA, COL I, and COL Ⅲ by Western blot.
RESULTS: ONSMP can effectively improve HF rat\'s cardiac function, decrease cardiac organ coefficient, COL volume fraction, and COL I/Ⅲ content, down-regulate the mRNA of COL I/Ⅲ, α-SMA and c-Fos, and the protein of p-RAS, p-RAF, p-MEK1/ 2, p-ERK1/2, p-ELK1, c-Fos, COL Ⅰ/Ⅲ, and α-SMA.
CONCLUSIONS: ONSMP can effectively reduce myocardial fibrosis in HF rats, and the mechanism may be related to the inhibition of the RAS/RAF/MEK/ERK signaling pathway.
摘要：
目的：探索优化的新生脉散（，ONSMP）基于大鼠肉瘤（RAS）/快速加速纤维肉瘤（RAF）/丝裂原活化蛋白激酶激酶（MEK）/细胞外调节蛋白激酶（ERK）信号通路对心力衰竭（HF）心肌纤维化的影响。
方法：将70只Sprague-Dawley大鼠随机分为假手术组（n=10）和手术组（n=60）。然后通过结扎冠状动脉左前降支建立HF大鼠。将手术组大鼠随机分为模型组,ONSMP[包括低(L),中等(M),和高（H）剂量]，和依那普利组。经过4周的药物干预，超声心动图检查心脏功能，并计算整个/左心脏与大鼠体重的比率。最后,通过病理切片观察心肌纤维化程度,酶联免疫吸附法测定心肌胶原(COL)Ⅰ和COLⅢ含量,检测COLI的mRNA水平，COLⅢ,α-平滑肌肌动蛋白（α-SMA），和c-Fos原癌基因(c-Fos)通过通用实时，并检测p-RAS的蛋白表达,p-RAF,p-MEK1/2,p-ERK1/2,p-ETS-like-1转录因子(p-ELK1),p-c-Fos,α-SMA,COLI,和COLⅢ的Westernblot。
结果：ONSMP能有效改善HF大鼠的心功能，降低心脏器官系数，COL体积分数,和COLI/Ⅲ含量，下调COLⅠ/Ⅲ的mRNA，α-SMA和c-Fos,和p-RAS的蛋白质，p-RAF,p-MEK1/2,p-ERK1/2,p-ELK1,c-Fos,COLⅠ/Ⅲ,和α-SMA。
结论：ONSMP能有效减轻HF大鼠心肌纤维化，其机制可能与抑制RAS/RAF/MEK/ERK信号通路有关。
方法：将70只Sprague-Dawley大鼠随机分为假手术组（n=10）和手术组（n=60）。然后通过结扎冠状动脉左前降支建立HF大鼠。将手术组大鼠随机分为模型组,ONSMP[包括低(L),中等(M),和高（H）剂量]，和依那普利组。经过4周的药物干预，超声心动图检查心脏功能，并计算整个/左心脏与大鼠体重的比率。最后,通过病理切片观察心肌纤维化程度,酶联免疫吸附法测定心肌胶原(COL)Ⅰ和COLⅢ含量,检测COLI的mRNA水平，COLⅢ,α-平滑肌肌动蛋白（α-SMA），和c-Fos原癌基因(c-Fos)通过通用实时，并检测p-RAS的蛋白表达,p-RAF,p-MEK1/2,p-ERK1/2,p-ETS-like-1转录因子(p-ELK1),p-c-Fos,α-SMA,COLI,和COLⅢ的Westernblot。
结果：ONSMP能有效改善HF大鼠的心功能，降低心脏器官系数，COL体积分数,和COLI/Ⅲ含量，下调COLⅠ/Ⅲ的mRNA，α-SMA和c-Fos,和p-RAS的蛋白质，p-RAF,p-MEK1/2,p-ERK1/2,p-ELK1,c-Fos,COLⅠ/Ⅲ,和α-SMA。
结论：ONSMP能有效减轻HF大鼠心肌纤维化，其机制可能与抑制RAS/RAF/MEK/ERK信号通路有关。
