硫化氢对心肌成纤维细胞增殖的抑制作用及机制研究  

Study on inhibitory effect and mechanism of hydrogen sulfide on the proliferation of cardiac fibroblasts

作　　者：刘露露 秦燕[1,2] 孟国梁 顾锦华 张琳[1] 包小燕 LIU Lulu;QIN Yan;MENG Guoliang;GU Jinhua;ZHANG Lin;BAO Xiaoyan(Dept.of Pharmacy,the Affiliated Maternity&Child Health Care Hospital of Nantong University/Nantong Children’s Hospital,Jiangsu Nantong 226007,China;School of Pharmacy,Nantong University,Jiangsu Nantong 226001,China;Electrocardiographic Room,the Affiliated Maternity&Child Health Care Hospital of Nantong University/Nantong Children’s Hospital,Jiangsu Nantong 226007,China)

机构地区：[1]南通大学附属妇幼保健院/南通市儿童医院药学部,江苏南通226007 [2]南通大学药学院,江苏南通226001 [3]南通大学附属妇幼保健院/南通市儿童医院心电图室,江苏南通226007

出　　处：《中国药房》2023年第4期438-443,共6页China Pharmacy

基　　金：江苏省333高层次人才培养工程[No(.2022)3-16-670号];南通市科技计划(指导性)项目(No.JCZ20167);南通市卫生健康委员会科研课题(No.QA2020034)。

摘　　要：目的研究硫化氢(H_(2)S)对心肌成纤维细胞增殖的抑制作用及机制。方法取新生SD雄性大鼠心脏,采用差速离心法分离心肌成纤维细胞。以硫氢化钠作为H_(2)S的供体,检测H_(2)S对血管紧张素Ⅱ(AngⅡ)诱导心肌成纤维细胞增殖、羟脯氨酸含量以及去乙酰化酶3(SIRT3)蛋白表达的影响。用干扰RNA技术下调SIRT3表达后,观察H_(2)S对AngⅡ诱导的心肌成纤维细胞增殖、羟脯氨酸的含量以及Ⅰ型胶原(ColⅠ)、Ⅲ型胶原(ColⅢ)和视神经萎缩蛋白1(OPA1)表达的影响。结果H_(2)S可抑制AngⅡ诱导的心肌成纤维细胞增殖,降低羟脯氨酸含量,增强SIRT3蛋白表达(P<0.05)。用干扰RNA技术下调SIRT3表达后,H_(2)S对AngⅡ诱导的心肌成纤维细胞增殖抑制作用、羟脯氨酸含量降低作用均被抑制,且H_(2)S降低ColⅠ、ColⅢ表达的作用和增强OPA1表达的作用也明显减弱。结论H_(2)S依赖增加SIRT3表达来抑制AngⅡ诱导的心肌成纤维细胞增殖。OBJECTIVE To investigate the inhibitory effect and the possible mechanism of hydrogen sulfide(H_(2)S)on the proliferation of cardiac fibroblasts.METHODS The heart of neonatal SD rats was collected,and cardiac fibroblasts were separated with differential centrifugation.Using sodium hydrosulfide as the donor of H_(2)S,the effects of H_(2)S on the proliferation of cardiac fibroblasts induced by angiotensinⅡ(AngⅡ),hydroxyproline content and the expression of sirtuin 3(SIRT3)protein were detected.After SIRT3 knockdown with siRNA technology,the effects of H_(2)S on the proliferation of cardiac fibroblasts induced by AngⅡ,hydroxyproline content,the expressions of collagenⅠ(ColⅠ),collagenⅢ(ColⅢ)and optic atrophy protein 1(OPA1)were detected.RESULTS H_(2)S could inhibit the proliferation of AngⅡ-induced cardiac fibroblasts,reduce the content of hydroxyproline and increase the expression of SIRT3(P<0.05).After down-regulating the expression of SIRT3 with siRNA technology,the inhibition of H_(2)S on the proliferation of AngⅡ-induced cardiac fibroblasts and the reduction of hydroxyproline content were both inhibited,and the effect of H_(2)S on reducing the expression of ColⅠand ColⅢand enhancing the expression of OPA1 was also significantly weakened.CONCLUSIONS H_(2)S inhibits the proliferation of AngⅡ-induced cardiac fibroblasts through increasing the expression of SIRT3.

关 键 词：硫化氢 心肌成纤维细胞 血管紧张素Ⅱ 去乙酰化酶3 

分 类 号：R965[医药卫生—药理学]