ObjectiveTo investigate the potential therapeutic effects of Dengzhan Shengmai capsules （DZSM） on myocardial fibrosis after myocardial infarction and decipher the underlying molecular mechanisms by virtue of network robustness algorithm. MethodsA rat model of myocardial infarction was established by ligating the left anterior descending coronary artery. Successfully modeled Sprague-Dawley rats were randomly allocated into a model group， an enalapril group（3.15 mg·kg^-1）， and high- and low-dose DZSM groups（226.8，113.4 mg·kg^-1）. In addition， a sham group was set up. After four consecutive weeks of intervention， the cardiac function was assessed via echocardiography， and myocardial collagen deposition was observed through Sirius red staining. The key regulatory pathways of DZSM were analyzed by the network robustness algorithm. Enzyme-linked immunosorbent assay （ELISA） and immunofluorescence assay were employed to validate the mechanisms. ResultsCompared with the sham group， the model group exhibited decreased left ventricular ejection fraction （LVEF%） and fractional shortening （FS%） （P<0.01） and increased myocardial collagen volume fraction （CVF%） （P<0.01）. Compared with the model group， high-dose DZSM and enalapril improved LVEF% and FS% （P<0.01）. Both high- and low-dose DZSM reduced the CVF% （P<0.05， P<0.05，）. Network analysis indicated that DZSM exerted its effects by regulating neutrophil infiltration and related inflammatory pathways. Experimental validation showed that DZSM significantly reduced the protein levels of nuclear factor （NF）-κB， Janus kinase 2 （JAK2）， and signal transduction activator and transducer 3 （STAT3） in the cardiac tissue， as well as the levels of chemokine （C-X-C motif） ligand 1 （CXCL1）， interleukin （IL）-1β， neutrophil elastase-DNA complex （NE-DNA）， and myeloperoxidase-DNA complex （MPO-DNA） in the plasma. ConclusionDZSM may ameliorate myocardial fibrosis by inhibiting neutrophil infiltration and extracellular trap formation and regulating the NF-κB/JAK2/STAT3 signaling pathway.

OBJECTIVE:To study the protective effect of butylphthalide on the apoptosis of human umbilical vein endothelial cells (HUVECs) induced by Aβ1-42 and its mechanism. METHODS:HUVECs were divided into normal control group,Aβ1-42 group,TAK242 group(10 nmol/L),DMSO group(1‰DMSO)and butylphthalide low-concentration,medium-concentration and high-concentration groups (40,80,160 μg/L). Except for normal control group and DMSO group,other groups were given 50 μmol/L Aβ1-42 to culture HUVECs for 24 h. TAK242 group,DMSO group and butylphthalide low-concentration,medium-concentra-tion and high-concentration groups were given relevant concentration of drugs for 30 min,with 3 holes for each concentration. The cell viability was determined by CCK-8 assay;cell apoptosis was observed by Hochest 33342/PI double staining;the cell apoptotic rate was detected by AnnexinⅤ-fluorescein isothiocyanate (FITC) flow cytometry;the protein expression of TLR-4 and COX-2 were determined by Western blot assay;the contents of IL-1 and TNF-α were detected by ELISA. RESULTS:Compared with nor-mal control group,cell viability of HUVECs were decreased in Aβ1-42 group;while apoptotic rate,protein expression of TLR4 and COX-2,the contents of IL-1 and TNF-α were increased. Compared with Aβ1-42 group,cell viability of HUVECs were increased in TAK242 group and butylphthalide low-concentration,medium-concentration and high-concentration groups;while apoptotic rate, protein expression of TLR4 and COX-2,the contents of IL-1 and TNF-α were decreased,with statistical significance(P<0.05 or P<0.01). CONCLUSIONS:Butylphthalide can reduce HUVECs apoptosis induced by Aβ1-42,which may be related with inhibiting the expression of TLR4,COX-2 and inflammatory factors.