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OBJECTIVE:Exploring the effect of Optimized New Shengmai powder(优化新生脉散方,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.