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。
Objective To investigate the effect of ginsenosides-Rbl(Gs-Rbl) on doxorubicin (Dox)-induced heart failure (HF), and the related mechanisms of connexin 43 (CX43) thereof. Methods Rats with Dox-induced HF were randomly divided into Dox group (n=lS) and Gs-Rbl group (n=17), and the health age-matched rats were as control (n=lS). In addition, cardiomyocytes were randomly divided into Dox group, Gs-Rbl group and control group. After the intervention, echocardiography or apoptotic ratio (ARi was analyzed, respectively. The expression levels of p21-activated kinase 1 (PAK1), protein phosphatase type 2A (PP2A) and CX43 were detected by Western bolt or RT-PCR analysis, respectively. Resuits Gs-Rbl significantly improved heart function in rats with HF, decreased left ventricular mass index and inhibited the cell apoptosis induced by Dox. Both mRNA and protein expressions of CX43 were significantly decreased in Dox group than those of control group. The expression of CX43 was significantly increased in Gs-Rbl group, which was significantly lower than that of control group. There was no significant difference in PAK1 between Dox group and control group (P 〉 0.05). The expression of PAK1 was significantly up-regulated by Gs-Rbl. The PP2A protein was significantly up-regulated in Dox group than that of control group, which was significantly higher in Gs-Rbl group than that of Dox group. Conclusion Gs-Rbl improved HF by adjusting CX43, which may be mediated by PAKI-PP2A.
出处
《天津医药》
CAS
北大核心
2013年第7期675-678,共4页
Tianjin Medical Journal
基金
辽宁省自然基金资助项目(项目编号:201102107)