天津医药

• 实验研究 •    

人参皂甙Rb1 对心力衰竭大鼠心肌缝隙连接蛋白 43 的影响

孔宏亮   

  1. 辽宁省人民医院心脏中心
  • 收稿日期:2012-11-05 修回日期:2013-02-21 出版日期:2013-07-15 发布日期:2013-07-15
  • 通讯作者: 孔宏亮

Effects of Ginsenosides-Rb1 on Connexin 43 in Heart Failure in Rats

KONG Hongliang   

  1. Cardiology Center, The People’ s Hospital of Liaoning Province, Shenyang 110016, China
  • Received:2012-11-05 Revised:2013-02-21 Published:2013-07-15 Online:2013-07-15
  • Contact: KONG Hongliang

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摘要：

【摘要】 目的  探讨人参皂甙Rb1(Gs-Rb1)改善阿霉素(Dox)所致心力衰竭(HF)效应是否与调整缝隙连接蛋白43(CX43)有关以及调节CX43的可能机制。方法  Dox诱导的HF大鼠被随机分为Dox组(n=15)和Gs-Rb1组[70mg/(kg·d),n=17],同龄健康鼠作为对照组(n=10);体外Dox干预的心肌细胞亦被随机分为Dox组、Gs-Rb1组和对照组。干预完成后,分别行心脏超声和流式细胞仪(FCM)检查;Westernbolt或RT-PCR检测p21蛋白活化激酶l(PAK1)、蛋白质磷酸酶-2A(PP2A)和CX43等的表达。结果  Gs-Rb1显著改善HF大鼠心功能、显著降低左室质量指数和显著降低Dox所致的心肌细胞凋亡。Dox组CX43mRNA和CX43蛋白显著低于对照组,而Gs-Rb1可显著升高CX43,但仍显著低于对照组。Dox组PAK1与对照组差异无统计学意义(P>0.05),而Gs-Rb1显著上调PAK1表达。Dox组PP2A的表达显著高于对照组,而Gs-Rb1组PP2A的表达显著高于Dox组。结论 Gs-Rb1通过调节CX43改善Dox的心肌损害效应,该效应可能受PAK1-PP2A调节。 

关键词: 人参皂甙Rbl, 心力衰竭, 连接蛋白43, 心肌, p21蛋白活化激酶l, 蛋白质磷酸酶-2A

Abstract: Objective    On the basis of doxorubicin(Dox)-induced heart failure (HF), the present study elucidated whether the effect of Ginsenosides-Rbl (Gs-Rb1), improving cardiac function, was performed by connexin 43 (CX43) and other mechanisms. Methods    Rats with Dox-induced HF were randomly divided into Dox group (n=15) and Gs-Rb1 group (n=17), and the health age-matched rat was as control (n=15); In addition, cardiomyocytes was randomly divided into Dox group, Gs-Rb1 group and control group, in vitro. After the above intervention being performed, echoeardiography or apoptosis ratio (AR) was analyzed, respectively. CX43, p21-activated kinase 1 (PAK2) and protein phosphatase type 2A (PP2A) was assayed by western bolt or Rt-PCR, respectively. Results    1. Gs-Rbl significantly improved LVEF (in vivo), markedly left ventricular weight index (in vivo) and significantly inhibited cell apoptosis (in vitro), all of which were induced by Dox; 2. Both mRNA and protein of CX43, being significantly decreased by Dox, were significantly up-regulated by Gs-Rbl, in vivo and in vitro; 3. There was no significance for PAK1 protein between Dox group and control group, which was markedly increased by Gs-Rbl, in vivo and in vitro; 4. PP2A protein was significantly up-regulated in Gs-Rbl group than in Dox group and in Dox group than in control group, in vivo and in vitro. Conclusion   The effect of Gs-Rb1, improving HF and inhibiting cell apoptosis, was partly performed through adjusting CX43 at least, which may be mediated by PAK1-PP2A.

Key words: Ginsenosides-Rbl, connexin 43, myocardium, p21-activated kinase 1, protein phosphatase type 2A