The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine （SAN） has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, a...The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine （SAN） has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, antitumor, and immune-enhancing properties. However, few studies have investigated the effects of SAN on lipopolysaceharide （LPS）-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes. Therefore, in this study, H9c2 cells were co-treated with SAN and LPS, and the mRNA levels of pro-inflammation markers and the apoptosis rate were measured to clarify the effect of SAN on cardiac inflammation. The underlying mechanism was further investigated by detecting the activation of Toll-like receptor （TLR）4/nuclear faetor-κB （NF-κB） signaling pathways. As a result, increased mRNA expression of interleukin （IL）-1β, IL-6, and TNFα induced by LPS was attenuated after SAN treatment; LPS-induced apoptosis ofHge2 cardiomyocytes and cleaved-caspase 8, 9, 3 were all significantly reduced by SAN. Further experiments showed that the beneficial effect of SAN on blocking the inflammation and apoptosis of H9c2 cardiomyocytes induced by LPS was associated with suppression of the TLR4/NF-κB signaling pathway. It was suggested that SAN suppressed the LPS-induced inflammation and apoptosis of H9c2 cardiomyocytes, which may be mediated by inhibition of the TLR4/NF-κB signaling pathway. Thus, SAN may be a feasible therapy to treat sepsis patients with cardiac dysfunction.展开更多
Bcl6,a critical pro-oncogene of human B-cell lymphomas,can promote tumor progress.Previous studies have found that Bcl6 participates in hypoxia injury in cardiomyocytes.However,the effect of Bcl6 on cardiac fibroblast...Bcl6,a critical pro-oncogene of human B-cell lymphomas,can promote tumor progress.Previous studies have found that Bcl6 participates in hypoxia injury in cardiomyocytes.However,the effect of Bcl6 on cardiac fibroblasts is still unclear.The aim of this study was to elucidate the functional role of Bcl6 in cardiac fibroblast activation and function.The neonatal rat cardiac fibroblasts were isolated and cultured.First,transforming growth factor β1 (TGFβ1) was used to stimulate fibroblast activation.A decreased expression level of Bcl6 was observed in fibroblasts after stimulation with TGFβ1.Then,cells were transfected with adenovirus Bcl6 to overexpress Bcl6.The results showed that Bcl6 overexpression induced decreased proliferation and reduced activation of fibroblasts which were stimulated with TGFβ1.It was found that activated smad2 and smad3 were not changed by overexpressing Bcl6,but smad4 was decreased.Furthermore,co-immunoprecipitation results showed that Bcl6 directly bound to smad4,and induced down-regulation of smad4.At last,smad4 activator could counteract the anti-fibroblast effects of Bcl6.In conclusion,Bcl6 may negatively regulate cardiac fibroblast activation and function by directly binding to smad4.展开更多
文摘The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine （SAN） has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, antitumor, and immune-enhancing properties. However, few studies have investigated the effects of SAN on lipopolysaceharide （LPS）-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes. Therefore, in this study, H9c2 cells were co-treated with SAN and LPS, and the mRNA levels of pro-inflammation markers and the apoptosis rate were measured to clarify the effect of SAN on cardiac inflammation. The underlying mechanism was further investigated by detecting the activation of Toll-like receptor （TLR）4/nuclear faetor-κB （NF-κB） signaling pathways. As a result, increased mRNA expression of interleukin （IL）-1β, IL-6, and TNFα induced by LPS was attenuated after SAN treatment; LPS-induced apoptosis ofHge2 cardiomyocytes and cleaved-caspase 8, 9, 3 were all significantly reduced by SAN. Further experiments showed that the beneficial effect of SAN on blocking the inflammation and apoptosis of H9c2 cardiomyocytes induced by LPS was associated with suppression of the TLR4/NF-κB signaling pathway. It was suggested that SAN suppressed the LPS-induced inflammation and apoptosis of H9c2 cardiomyocytes, which may be mediated by inhibition of the TLR4/NF-κB signaling pathway. Thus, SAN may be a feasible therapy to treat sepsis patients with cardiac dysfunction.
文摘Bcl6,a critical pro-oncogene of human B-cell lymphomas,can promote tumor progress.Previous studies have found that Bcl6 participates in hypoxia injury in cardiomyocytes.However,the effect of Bcl6 on cardiac fibroblasts is still unclear.The aim of this study was to elucidate the functional role of Bcl6 in cardiac fibroblast activation and function.The neonatal rat cardiac fibroblasts were isolated and cultured.First,transforming growth factor β1 (TGFβ1) was used to stimulate fibroblast activation.A decreased expression level of Bcl6 was observed in fibroblasts after stimulation with TGFβ1.Then,cells were transfected with adenovirus Bcl6 to overexpress Bcl6.The results showed that Bcl6 overexpression induced decreased proliferation and reduced activation of fibroblasts which were stimulated with TGFβ1.It was found that activated smad2 and smad3 were not changed by overexpressing Bcl6,but smad4 was decreased.Furthermore,co-immunoprecipitation results showed that Bcl6 directly bound to smad4,and induced down-regulation of smad4.At last,smad4 activator could counteract the anti-fibroblast effects of Bcl6.In conclusion,Bcl6 may negatively regulate cardiac fibroblast activation and function by directly binding to smad4.
