人参皂甙Rb1对心力衰竭大鼠蛋白激酶R样内质网激酶途径的影响

目的探讨人参皂甙Rbl（Gs—Rbl）改善阿霉素所致心力衰竭（HF）效应是否与调整蛋白激酶R样内质网激酶（PERK）通路有关。方法阿霉素（Adr）诱导的HF大鼠随机分为HF组（n=15）和Gs．Rbl组（70rng／kg／d，n=17），另随机选取同龄大鼠作为对照组（n=10）。干预结束并进行心脏超声检查后，TUNNEL检测心肌细胞凋亡率（AR），Western blot和Rt-PCR检测葡萄糖调节蛋白78（GRP78）、PERK、p-PERK、真核细胞起始因子2-（elF2a）、p-elF2a、C／EBP同源蛋白（CHOP）和cleavedcaspase-12。结果1．Adr干预成功构建HF模型，Gs—Rbl显著提高左室射血分数（LVEF）和降低心肌细胞AR（P〈O．01）；2．HF组GRP78mRNA和蛋白均显著高于对照组，Gs—Rbl显著低于HF组和对照组二组的表达（P〈0．01）；3．Gs—Rbl显著降低HF大鼠PERK和p-PERK表达（P〈0．01）；4．HF导致elF2amRNA和蛋白、p-elF2a显著升高，Gs—Rbl显著下调三者的表达（P〈O．01）；5．HF组CHOPmRNA和蛋白显著高于对照组，Gs—Rbl组显著抑制其表达（P〈0．01）；6．Gs—Rbl显著抑制阿霉素所致的caspase-121TIRNA和cleaved caspase-12蛋白表达（P〈0．01）。结论Gs—Rbl通过调节PERK内质网通路介导其改善HF效应。

Ginsenosides-Rbl improves adriamycin-induced heart failure by adjusting the protein kinase R-like ER kinase pathway

Objective Based on adrlamycm-lnduced heart Iallure taP）, me present stuay eiuctoateo whether the effect of Ginsenosides-Rhl （Gs-Rbl） improving cardiac function was performed by inhibiting protein kinase R-like ER kinase （PERK） pathway. Methods Rats with Adr-induced HF were randomly di- vided into HF group （n-----15） and Gs-Rbl group （n=17）, and healthy age-matched rats served as control （n-----10）. After the intervention was performed and the left ventricular ejection fraction （LVEF） was ana- lyzed by echocardiography, cell apoptosis ratio （AR）, glucose-regulated protein 78 （GRP78）, protein ki- nase R-like ER kinase （PERK）, p-PERK, eukaryotic initiation factor 2 （eIF2）, p-elF2a, C/EBP homol- ogous protein （CHOP） and caspase-12 were assayed, respectively. Reaulta 1. HF was induced by Adr; LVEF was significantly improved by Gs-Rbl （P〈0.01）. 2. Both mRNA and protein of GRP78 were sig- nificantly up-regulated in HF group than in control group （P〈0.01）, which were significantly down-regu- lated in Gs-Rbl group than in HF group （P〈0.01）. 3. Both PERK and p-PERK were significantly inhibi- ted by Gs-Rbl, compared with HF group （P〈0.01）. 4. eIF2a mRNA, eIF2a protein and p-eIF2a protein, being significantly up-regulated by Adr, were markedly down-regulated by Gs-Rbl. 5. Both mRNA and protein of CHOP were significantly higher in HF group than in control group （P〈0. 01）, which were significantly lower in Gs-RB1 group than in HF group （P〈0.01）. 6. Both mRNA and protein of caspase-12, being significantly in- creased in HF group （P〈0.01）, were markedly decreased by Gs-Rbl （P〈0.01）. Conclusion The effect of Gs-Rhl, improving HF, was at least partly fulfilled by adjusting the PERK pathway.