Paeoniflorin attenuates pressure overload-induced cardiac remodeling via inhibition of TGFβ/Smads and NF-κB pathways
Paeoniflorin attenuates pressure overload-induced cardiac remodeling via inhibition of TGFβ/Smads and NF-κB pathways
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DOI：
10.1007/s10735-013-9491-x
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发表时间：
2013-06-01
影响因子：
3.2
通讯作者：
Tang, Qi-Zhu
中科院分区：
文献类型：
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作者：
Zhou, Heng;Yang, He-Xin;Tang, Qi-Zhu
心脏重构是心力衰竭临床病程和转归的关键决定因素，以心肌肥大、纤维化、心肌细胞凋亡和炎症为特征。芍药苷的抗炎、抗凋亡和抗纤维化作用已在不同类型的组织和细胞中得到鉴定。然而，芍药苷在心脏重塑中的作用尚不清楚。我们对小鼠实施了主动脉缩窄(AB)，以诱导压力超负荷所致的心脏重塑模型。芍药苷(20 mg/kg)每日腹腔注射(Ip)。注射。术后8周，用药组小鼠存活率提高，心功能改善。用心脏重量、心脏大体、HE和WGA染色、心肌细胞横截面积和肥大标志物的mRNA表达来评价AB诱导的心肌肥厚，可以被芍药苷所减轻。芍药苷还能抑制压力超负荷心脏胶原沉积、转化生长因子β、结缔组织生长因子、I型胶原和III型胶原的表达，抑制Smad2和Smad3的磷酸化。芍药苷可抑制AB诱导的心肌细胞凋亡及Bax和裂解caspase3的表达。此外，芍药苷还能降低AB后心脏CD68+细胞数量、IL-1β和TNF-α的蛋白水平，以及I-kappa Bα和NF-kappa B-p65的磷酸化水平。总而言之，芍药苷可减轻压力超负荷小鼠的心肌肥大、纤维化、细胞凋亡和炎症反应，改善左心功能。芍药苷的心脏保护作用与抑制转化生长因子β/Smads和核因子-kappaB通路有关。
Cardiac remodeling is a key determinant in the clinical course and outcome of heart failure and characterized by cardiac hypertrophy, fibrosis, cardiomyocyte apoptosis and inflammation. The anti-inflammatory, anti-apoptotic and anti-fibrotic effects of paeoniflorin have been identified in various types of tissue and cells. However, the role of paeoniflorin in cardiac remodeling remains unclear. We performed aortic banding (AB) in mice to induce a cardiac remodeling model in response to pressure overload. Paeoniflorin (20 mg/kg) was administered by daily intraperitoneal (i.p.) injection. Paeoniflorin treatment promoted the survival rate and improved cardiac function of mice at 8 weeks post surgery. AB-induced cardiac hypertrophy, as assessed by heart weight, gross heart, HE and WGA staining, cross-sectional area of cardiomyocyte and mRNA expresssion of hypertrophic makers, was attenuated by paeoniflorin. Paeoniflorin also inhibited collagen deposition, expression of TGF beta, CTGF, collagen I alpha and collagen III alpha, and phosphorylation of Smad2 and Smad3 in the heart exposed to pressure overload. Cardiomyocyte apoptosis and induction of Bax and cleaved caspase3 in response to AB were suppressed by paeoniflorin. Furthermore, paeoniflorin decreased the quantity of CD68+ cells, protein levels of TNF-alpha and IL-1 beta, and phosphorylation of I kappa B alpha and NF kappa B-p65 in the heart after AB. In conclusion, paeoniflorin attenuated cardiac hypertrophy, fibrosis, apoptosis and inflammation, and improved left ventricular function in pressure overloaded mice. The cardioprotective effect of paeoniflorin is associated with the inhibition of TGF beta/Smads and NF-kappa B pathways.