亚精胺通过抑制音猬因子信号通路减轻心肌胶原沉积和氧化应激作用  

Effects of Spermine on Attenuating Myocardial Collagen Deposition and Oxidative Stress via Inhibiting SHH Signaling Pathway

作　　者：王莉[1] 刘敏[1] WANG Li;LIU Min(Gerontology Research Center,the Affiliated Hospital of Jianghan University,Wuhan 430014,China)

机构地区：[1]江汉大学附属医院老年医学研究所,武汉430014

出　　处：《医药导报》2022年第9期1276-1281,共6页Herald of Medicine

基　　金：湖北省卫生健康科研基金资助项目(WJ2019M002)。

摘　　要：目的探讨亚精胺对心肌胶原沉积和氧化应激的改善作用及其机制。方法采用50 mol·L^(-1) D-半乳糖诱导大鼠心肌细胞H9c2胶原沉积和氧化应激,分为模型对照组、20μmol·L^(-1)亚精胺组、50μmol·L^(-1)亚精胺组、50μmol·L^(-1)亚精胺+3 nmol·L^(-1)音猬因子(SHH)信号通路激动剂组(SAG组),另设正常对照组。通过检测细胞羟脯氨酸含量和胶原mRNA水平评价胶原沉积情况;检测总抗氧化能力、抗氧化酶活力、丙二醛和细胞内活性氧(ROS)含量评价氧化应激程度;检测SHH信号通路节点蛋白的表达量以及下游转化生长因子(TGF)-β_(1)的mRNA水平评价SHH信号通路活跃程度;检测上皮-间质转化(EMT)标记物的mRNA水平评价EMT水平。结果与正常对照组比较,D-半乳糖刺激显著增加了H9c2细胞的羟脯氨酸含量、胶原的mRNA水平,以及SHH信号通路各节点蛋白的表达量,并促进氧化应激和EMT(P<0.01)。与模型对照组比较,20和50μmol·L^(-1)亚精胺均显著抑制了H9c2的胶原沉积、氧化应激、EMT和SHH信号通路(P<0.01)。与50μmol·L^(-1)亚精胺组比较,SAG组在一定程度上抵消了亚精胺的上述作用。结论亚精胺能够通过抑制SHH信号通路减轻心肌胶原沉积和氧化应激,对改善心脏衰老具有潜在的应用价值。Objective To investigate the effects and mechanisms of spermidine on attenuating myocardial collagen deposition and oxidative stress.Methods The collagen deposition and oxidative stress of rats cardiomyocytes H9c2 were induced by 50 mol·L^(-1) D-galactose.The cells were divided into D-galactose model control group,20μmol·L^(-1) and 50μmol·L^(-1) spermidine groups,as well as 50μmol·L^(-1) spermidine+3 nmol·L^(-1) sonic hedgehog(SHH)signaling pathway agonist group(SAG group).Additionally,a vehicle control group was set.The collagen deposition was evaluated by measuring the levels of hydroxyproline and the mRNA levels of collagens.The oxidative stress was evaluated by measuring the level total antioxidant capacity,the activities of antioxidant enzymes,the contents of malondialdehyde and reactive oxygen species.The activity of SHH signaling pathway was evaluated by measuring the expression of node proteins,and the mRNA level of downstream target transforming growth factor(TGF)-β_(1).The epithelial-mesenchymal transition(EMT)was evaluated by measuring the mRNA levels of EMT markers.Results When compared to the vehicle control,D-galactose significantly(P<0.01)increased the content of hydroxyproline and mRNA levels of collagens,enhanced the expression of SHH signaling pathway node proteins,promoted oxidative stress and EMT in H9c2 cells.When compared to the D-galactose model control group,both 20μmol·L^(-1) and 50μmol·L^(-1) spermidine significantly(P<0.01)inhibited the collagen deposition,oxidative stress,EMT and SHH signaling pathway in H9c2.When compared to the 50μmol·L^(-1) spermidine group,co-treated with SAG alleviated these protective effects of spermidine.Conclusion Spermidine can attenuate D-galactose-induced myocardial collagen deposition and oxidative stress via inhibiting SHH signaling pathway,and thus has the potential application value in alleviating heart aging.

关 键 词：亚精胺 心肌胶原沉积 上皮-间质转化 氧化应激 音猬因子信号通路 

分 类 号：R972[医药卫生—药品] R592[医药卫生—药学]