黄芪甲苷通过激活短链酰基辅酶A脱氢酶抑制Ang Ⅱ诱导的大鼠心肌成纤维细胞增殖和胶原表达  

Astragaloside Ⅳ inhibits Ang Ⅱ-induced cell proliferation and collagen expression in cardiac fibroblasts by activating short-chain acyl-CoA dehydrogenase

作　　者：刘兰婷 徐庆萍 彭欢 沈千惠 贾康 卿丽媛 周四桂 LIU Lan-ting;XU Qing-ping;PENG Huan;SHEN Qian-hui;JIA Kang;QING Li-yuan;ZHOU Si-gui(School of Chinese Materia Medica,Guangdong Pharmaceutical University,Guangzhou 510006,China;Key Specialist Dept of Clinical Pharmacy,the First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou 510699,China)

机构地区：[1]广东药科大学中药学院,广东广州510006 [2]广东药科大学附属第一医院临床药学重点专科,广东广州510699

出　　处：《中国药理学通报》2023年第8期1450-1456,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81670239);广东省普通高校重点领域专项(No 2021ZDZX2019)。

摘　　要：目的观察黄芪甲苷(astragaloside Ⅳ,AS-Ⅳ)对血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)诱导的大鼠心肌成纤维细胞(cardiac fibroblasts,CFs)增殖和胶原表达的影响。方法原代提取并体外培养大鼠CFs,用短链酰基辅酶A脱氢酶(short-chain acyl-CoA dehydrogenase,SCAD)的沉默基因SiRNA1186预处理CFs 12 h后,加入Ang Ⅱ和AS-Ⅳ共同处理36 h。Western blot检测SCAD、α-SMA、collagen Ⅰ、collagen Ⅲ的蛋白表达水平;荧光定量PCR检测SCAD、α-SMA、collagen Ⅰ、collagen Ⅲ的mRNA表达水平;检测各组CFs中SCAD酶活性、ATP、羟脯氨酸和游离脂肪酸含量变化。结果Ang Ⅱ作用CFs 36 h后,与空白对照组比较,Ang Ⅱ组CFs增殖率,α-SMA、Collagen Ⅰ、Collagen Ⅲ的蛋白和mRNA表达水平明显增加(P均<0.01),SCAD表达和酶活性均明显降低(P<0.01,P<0.05),ATP生成减少(P<0.01),羟脯氨酸和游离脂肪酸含量升高(P均<0.01);AS-Ⅳ给药处理后,CFs增殖和胶原表达明显减少(P均<0.01),SCAD表达和酶活性明显升高(P均<0.01),ATP生成增加(P<0.01),羟脯氨酸和游离脂肪酸含量减少(P均<0.01);然而,与Ang Ⅱ+NC组相比,Ang Ⅱ+SiRNA1186+AS-Ⅳ组各项指标均无差异,在SCAD SiRNA1186的干扰下,AS-Ⅳ对Ang Ⅱ诱导的CFs增殖和胶原表达的保护作用被取消。结论AS-Ⅳ可能通过激活SCAD,从而抑制Ang Ⅱ诱导的大鼠心肌成纤维细胞增殖和胶原表达。Aim To explore the effect of astragaloside Ⅳ(AS-Ⅳ)on cell proliferation and collagen expression in cardiac fibroblasts(CFs)of rats induced with angiotensin Ⅱ(AngⅡ)and its mechanism.Methods CFs were pretreated with short-chain acyl-CoA dehydrogenase(SCAD)siRNA1186 for 12 h and then co-treated with Ang Ⅱ and AS-Ⅳ for 36 h.The expressions of SCAD,α-SMA,collagen Ⅰ and collagen Ⅲ in CFs were detected by Western blot.mRNA expression levels of SCAD,α-SMA,collagen Ⅰ and collagen Ⅲ in CFs were detected by quantitative real-time PCR.The SCAD enzymatic activity,the content of ATP,hydroxyproline and free fatty acid were measured by detection kits.Results The expression of α-SMA,collagen Ⅰ and collagen Ⅲ were up-regulated(all P<0.01)in CFs induced by Ang Ⅱ compared with the control cells,and the expression and enzymatic activity of SCAD significantly decreased(P<0.01,P<0.05).The content of ATP decreased(P<0.01),and the content of hydroxyproline and free fatty acids increased(all P<0.01).Compared with Ang Ⅱ group,SCAD expression and enzymatic activity,and ATP content were significantly increased(all P<0.01)in Ang Ⅱ+AS-Ⅳ group,but the content of hydroxyproline and free fatty acids,and the expression ofα-SMA,collagen Ⅰ and collagen Ⅲ significantly decreased(all P<0.01).However,compared with the AngⅡ+NC group,there was no significant difference in all indices in the Ang Ⅱ+SiRNA1186+AS-Ⅳ group.The protective effect of AS-Ⅳ on Ang Ⅱ-induced cell proliferation and collagen expression in CFs was eliminated by the interference of SCAD SiRNA1186.Conclusions AS-Ⅳmay inhibit Ang Ⅱ-induced cell proliferation and collagen expression in CFs by activating SCAD.

关 键 词：黄芪甲苷 短链酰基辅酶A脱氢酶 心肌成纤维细胞 血管紧张素Ⅱ 心肌纤维化 能量代谢 

分 类 号：R-332[医药卫生] R284.1R322.11R345.4R349.1R542.23