三七总皂苷通过TLR4/NF-кB信号通路抑制异丙肾上腺素诱导的心肌细胞肥大  

Panax notoginseng saponins attenuate ISO-induced cardiomyocytes hypertrophy via Toll-like receptor 4 /nuclear factor-κB signal pathway

作　　者：王卉[1,2] 杨育红[1] 庞子为 王洪新[1] 

机构地区：[1]辽宁医学院药理教研室,锦州121001 [2]盘锦市中心医院,盘锦124000 [3]大连理工大学化工与环境生命学部,大连116085

出　　处：《中药药理与临床》2014年第2期58-62,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然基金资助项目(30973898/C190702);辽宁省科技计划项目(2009225010-40)

摘　　要：目的 :探讨三七总皂苷(PNS)在异丙肾上腺素(ISO)诱导心肌细胞肥大中的保护作用及其机制。方法:离体培养SD乳鼠心肌细胞,用10μmol/L异丙肾上腺素诱导心肌细胞肥大,观察5μmol/L BAY11-7082(核因子-кB特异性抑制剂)及不同剂量三七总皂苷(12.5 mg/L,25 mg/L,50 mg/L)对肥大心肌细胞的影响。采用计算机图像分析系统测量细胞体积;考马斯亮蓝法测心肌细胞总蛋白含量;酶联免疫吸附法检测细胞外液中肿瘤坏死因子-α(TNF-α)的含量;反转录-PCR法检测ANP mRNA的表达;蛋白质印迹法检测心肌细胞TLR4和IκBα蛋白的表达。结果:与正常对照组相比,异丙肾上腺素模型组心肌细胞体积、总蛋白含量、ANP mRNA的表达、炎症因子TNF-α的含量及TLR4蛋白的表达均明显增高,而IκBα蛋白表达明显降低。三七总皂苷和BAY11-7082均能有效抑制异丙肾上腺素诱导的肥大反应及炎症反应,表现为细胞体积、总蛋白含量、ANP mRNA表达、细胞外液中TNF-α含量、TLR4蛋白表达均明显降低,IκBα蛋白含量显著增高。结论 :三七总皂苷对异丙肾上腺素诱导乳鼠心肌细胞肥大具有保护作用,其机制可能与抑制TLR4/NF-κB信号通路,减少炎症反应有关。Objective： To discuss the effects and mechanism of Panax notoginseng saponins（ PNS） on cardiomyocytes hypertrophy induced by isoproterenol（ ISO）. Methods： Cardiomyocytes isolated from SD neonatal rats and the hypertrophic response was induced by 10 μmol /L ISO.The effects of 5 μmol /L BAY11-7082 and different concentrations of PNS（ 12. 5 mg /L,25 mg /L,50 mg /L） on hypertrophic cardiomyocytes were observed. The volume of cardiomyocyte was measured by computer photograph analysis system; total protein content was determined by Bradford; expression of TNF-α was assayed by ELISA; expression of ANP mRNA was measured by RT-PCR; expression of TLR4 and IκBαprotein expression were assayed by Western blot. Results： Compared with the normal control group,the cardiomyocyte size,total protein content,ANP mRNA expression,level of TNF-α and TLR4 protein were significantly increased（ P ＆lt; 0. 01）,but IкBα expression was markedly decreased（ P ＆lt; 0. 01） in ISO group. BAY11-7082 and APS could inhibit the hypertrophic response and inflammation induced by ISO,expressed as the down-regulation of cell volume,total protein content,expression of ANP mRNA,level of TNF-α and TLR4 protein expression,and the up-regulation of IкBα protein expression. Conclusion： PNS could attenuate cardiomyocytes hypertrophy and inflammation induced by ISO,and the mechanism may relate to TLR4 /NF-κB inflammatory signaling pathway.

关 键 词：三七总皂苷 异丙肾上腺素 心肌细胞 TOLL样受体4 核因子-ΚB 炎症 

分 类 号：R285[医药卫生—中药学]