Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium / 中国结合医学杂志

OBJECTIVE@#To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.@*METHODS@#A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.@*RESULTS@#DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).@*CONCLUSION@#DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.

Effectiveness and Safety of Chinese Medicinal Injection in Treatment of Unstable Angina Pectoris Based on Network Meta-analysis / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the clinical effectiveness and safety of Chinese medicinal injection （CMI） in the treatment of unstable angina pectoris （UAP）. MethodEight databases， i.e.， China National Knowledge Infrastructure （CNKI），VIP，Wanfang Data，CBM，PubMed，EMBASE，The Cochrane Library，and Web of Science were searched for randomized controlled trials （RCT） of conventional treatment combined with CMI （treatment group） versus conventional treatment （CT）（control group）in the treatment of UAP published from database inception to March 31th 2021. Stata 16.0 was used for network Meta-analysis. ResultThirty-nine RCT involving 3 407 patients were included. As revealed by the results of network Meta-analysis， in terms of the total effective rate in angina pectoris improvement， the therapeutic protocols were ranked as Tanreqing injection（TRQI）+CT>Xiangdan injection（XDI）+CT>Ciwujia injection（CWJI）+CT=Shengmai injection（SMI）+CT>Xuesaitong injection（XSTS）+CT>Breviscapine injection（BI）+CT>Shuxuetong injection（SXTI）+CT>Kudiezi injection（KDZI）+CT>Shuxuening injection（SXNI）+CT>Danshen injection （DSI）+CT>Guanxinning injection（GXNI）+CT>Dengzhanxixin injection（DZXXI）+CT>Xueshuantong injection（XSTI）+CT>Gualoupi injection（GLPI）+CT>CT；for the total effective rate in ECG improvement， SXTI+CT>XDI+CT>TRQI+CT>CWJI+CT>XSTI+CT>BI+CT>XSTI+CT>SXNI+CT>GXNI+CT>KDZI+CT>DZXXI+CT>GLPI+CT>CT>SMI+CT；for the adverse reactions， DZXXI+CT>XDI+CT>DSI+CT>BI+CT>SMI+CT>SXNI+CT>CT>GLPI+CT>GXNI+CT>SXTI+CT>KDZI+CT>CWJI+CT；for the reduction of fibrinogen （FIB）， BI+CT>SXTI+CT>XSTI+CT>CT>KDZI+CT；for the reduction of C-reactive protein （CRP）， DSI+CT>DZXXI+CT>XSTI+CT>CT；for the reduction of high-sensitivity C-reactive protein （hs-CRP）， SXNI+CT>KDZI+CT>SXTI+CT>DZXXI+CT>GLPI+CT>TRQI+CT>XSTI+CT>CT. The results of subgroup analyses were consistent with those of the overall Meta-analysis. ConclusionCMI combined with CT can improve angina pectoris and ECG，reduce adverse reactions，and also improve FIB，CRP，and hs-CRP to varying degrees. However，due to the differences in the quality and quantity of CMIs in RCTs，clinical application should be performed based on the specific conditions.