Pathological cardiac hypertrophy induced by angiotensin Ⅱ （Ang Ⅱ ） can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the r...Pathological cardiac hypertrophy induced by angiotensin Ⅱ （Ang Ⅱ ） can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the roots ofNardostachys chinensis, a well-known traditional Chinese medicine. In order to investigate the effects of nardosinone on Ang Ⅱ-induced cardiac cell hypertrophy and the related mechanisms, the myoblast cell line H9c2, derived from embryonic rat heart, was treated with nardosi- none （25, 50, 100, and 200μmol/L） or Ang Ⅱ （1 μmol/L）. Then cell surface area and mRNA expression of classical markers of hypertrophy were detected. The related protein levels in PI3K/Akt/mTOR and MEK/ERK signaling pathways were examined by Western blotting. It was found that pretreatment with nardosinone could significantly inhibit the enlargement of cell surface area induced by Ang Ⅱ. The mRNA expression of ANP, BNP and 13-MHC was obviously elevated in Ang Ⅱ-treated H9c2 cells, which could be effectively blocked by nardosinone at the concentration of 100μmol/L. Further study revealed that the protective effects of nardosinone might be mediated by repressing the phosphorylation of related proteins in PI3K/Akt and MEK/ERK signaling pathways. It was suggested that the inhibitory effect of nardosinone on Ang Ⅱ-induced hypertrophy in H9c2 cells might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways.展开更多
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
基金supported by the grants from the National Natural Science Foundation of China(No.30971245 and No.81000112)
文摘Pathological cardiac hypertrophy induced by angiotensin Ⅱ （Ang Ⅱ ） can subsequently give rise to heart failure, a leading cause of mortality. Nardosinone is a pharmacologically active compound extracted from the roots ofNardostachys chinensis, a well-known traditional Chinese medicine. In order to investigate the effects of nardosinone on Ang Ⅱ-induced cardiac cell hypertrophy and the related mechanisms, the myoblast cell line H9c2, derived from embryonic rat heart, was treated with nardosi- none （25, 50, 100, and 200μmol/L） or Ang Ⅱ （1 μmol/L）. Then cell surface area and mRNA expression of classical markers of hypertrophy were detected. The related protein levels in PI3K/Akt/mTOR and MEK/ERK signaling pathways were examined by Western blotting. It was found that pretreatment with nardosinone could significantly inhibit the enlargement of cell surface area induced by Ang Ⅱ. The mRNA expression of ANP, BNP and 13-MHC was obviously elevated in Ang Ⅱ-treated H9c2 cells, which could be effectively blocked by nardosinone at the concentration of 100μmol/L. Further study revealed that the protective effects of nardosinone might be mediated by repressing the phosphorylation of related proteins in PI3K/Akt and MEK/ERK signaling pathways. It was suggested that the inhibitory effect of nardosinone on Ang Ⅱ-induced hypertrophy in H9c2 cells might be mediated by targeting PI3K/Akt and MEK/ERK signaling pathways.
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.
文摘目的:探讨N-乙酰半胱氨酸(NAC)抑制亚砷酸钠诱导H9C2细胞凋亡和自噬作用及机制。方法:用亚砷酸钠诱导H9C2细胞构建凋亡和自噬模型。采用CCK-8比色法检测细胞的存活率,Hoechst 33258核染色法观察凋亡细胞的形态和数量改变.双氯荧光素染色法检测细胞内活性氧(ROS)水平,Western Blot法测定蛋白P53、Bcl-2、Bax及LC3的表达水平,以及磷酸化ERK1/2蛋白及ERK1/2蛋白总量的表达水平。结果:与对照组相比,15μM亚砷酸钠处理的H9C2细胞存活率显著降低.细胞内ROS水平明显增加.凋亡细胞数量明显增多,自噬标志蛋白LC3-Ⅱ与LC3-Ⅰ比值明显增大(P<0.01)。1 mM NAC预处理后显著减少H9C2细胞内ROS的生成和促凋亡蛋白P53和Bax的表达,诱导抗凋亡蛋白Bcl-2表达升高,同时降低自噬相关蛋白LC3-Ⅱ与LC3-Ⅰ的比值。亚砷酸钠处理诱导ERK1/2蛋白磷酸化(P<0.01),而NAC和亚砷酸钠共处理抑制了ERK1/2蛋白的磷酸化。结论:亚砷酸钠降低H9C2细胞的存活率,增加细胞内ROS的生成,诱导细胞凋亡和自噬。NAC通过降低H9C2细胞内的ROS水平和抑制ERK1/2蛋白的磷酸化拮抗亚砷酸钠诱导的细胞凋亡和自噬。
