天津医药
天津醫藥
천진의약
TIANJIN MEDICAL JOURNAL
2013年
7期
675-678
,共4页
孔宏亮%李占全%苗志林%叶丽萍
孔宏亮%李佔全%苗誌林%葉麗萍
공굉량%리점전%묘지림%협려평
人参皂甙%心力衰竭%连接蛋白类%心肌%蛋白质磷酸酶2%p21蛋白活化激酶1
人參皂甙%心力衰竭%連接蛋白類%心肌%蛋白質燐痠酶2%p21蛋白活化激酶1
인삼조대%심력쇠갈%련접단백류%심기%단백질린산매2%p21단백활화격매1
GINSENOSIDE%heart failure%connexins%myocardium%protein phosphatase 2%p21-activated kinase 1
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[70 mg/(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;Western bolt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CX43 mRNA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。
目的探討人參皂甙Rb1(Gs-Rb1)改善阿黴素(Dox)所緻心力衰竭(HF)效應是否與調整縫隙連接蛋白43(CX43)有關以及調節CX43的可能機製。方法 Dox誘導的HF大鼠被隨機分為Dox組(n=15)和Gs-Rb1組[70 mg/(kg·d), n=17],同齡健康鼠作為對照組(n=10);體外Dox榦預的心肌細胞亦被隨機分為Dox組、Gs-Rb1組和對照組。榦預完成後,分彆行心髒超聲和流式細胞儀(FCM)檢查;Western bolt或RT-PCR檢測p21蛋白活化激酶l (PAK1)、蛋白質燐痠酶-2A (PP2A)和CX43等的錶達。結果 Gs-Rb1顯著改善HF大鼠心功能、顯著降低左室質量指數和顯著降低Dox所緻的心肌細胞凋亡。Dox組CX43 mRNA和CX43蛋白顯著低于對照組,而Gs-Rb1可顯著升高CX43,但仍顯著低于對照組。Dox組PAK1與對照組差異無統計學意義(P>0.05),而Gs-Rb1顯著上調PAK1錶達。Dox組PP2A的錶達顯著高于對照組,而Gs-Rb1組PP2A的錶達顯著高于Dox組。結論 Gs-Rb1通過調節CX43改善Dox的心肌損害效應,該效應可能受PAK1-PP2A調節。
목적탐토인삼조대Rb1(Gs-Rb1)개선아매소(Dox)소치심력쇠갈(HF)효응시부여조정봉극련접단백43(CX43)유관이급조절CX43적가능궤제。방법 Dox유도적HF대서피수궤분위Dox조(n=15)화Gs-Rb1조[70 mg/(kg·d), n=17],동령건강서작위대조조(n=10);체외Dox간예적심기세포역피수궤분위Dox조、Gs-Rb1조화대조조。간예완성후,분별행심장초성화류식세포의(FCM)검사;Western bolt혹RT-PCR검측p21단백활화격매l (PAK1)、단백질린산매-2A (PP2A)화CX43등적표체。결과 Gs-Rb1현저개선HF대서심공능、현저강저좌실질량지수화현저강저Dox소치적심기세포조망。Dox조CX43 mRNA화CX43단백현저저우대조조,이Gs-Rb1가현저승고CX43,단잉현저저우대조조。Dox조PAK1여대조조차이무통계학의의(P>0.05),이Gs-Rb1현저상조PAK1표체。Dox조PP2A적표체현저고우대조조,이Gs-Rb1조PP2A적표체현저고우Dox조。결론 Gs-Rb1통과조절CX43개선Dox적심기손해효응,해효응가능수PAK1-PP2A조절。
Objective To investigate the effect of ginsenosides-Rb1(Gs-Rb1) on doxorubicin (Dox)-induced heart failure (HF), and the related mechanisms of connexin 43 (CX43) thereof. Methods Rats with Dox-induced HF were ran-domly divided into Dox group (n=15) and Gs-Rb1 group (n=17), and the health age-matched rats were as control (n=15). In addition, cardiomyocytes were randomly divided into Dox group, Gs-Rb1 group and control group. After the intervention, echocardiography or apoptotic ratio (AR) 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. Re-sults Gs-Rb1 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-Rb1 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-Rb1. The PP2A protein was significantly up-regulated in Dox group than that of control group, which was significantly higher in Gs-Rb1 group than that of Dox group. Conclusion Gs-Rb1 improved HF by adjusting CX43, which may be mediated by PAK1-PP2A.