人参皂甙Rbl对阿霉素心力衰竭大鼠心肌细胞Toll样受体的影响

摘要

目的：探讨人参皂甙Rbl （Gs-Rb1）减轻阿霉素所致的慢性心力衰竭（CHF）效应是否与抑制 Toll样受体（TLRs）有关。方法：阿霉素慢性心力衰竭（CHF）大鼠随机分为阿霉素组（15例）和Gs-Rbl组（70 mg/kg · d ，17例），另设正常对照组（10例）。乳鼠心肌细胞亦随机分为对照组、阿霉素组（1μmol/L ）和 Gs-Rbl组（1μmol/L阿霉素＋200μmol/L Gs-Rbl）。干预完毕后，评定心脏超声， Toll样受体2和 Toll样受体4蛋白和基因。结果：（1）体内、体外研究均显示，阿霉素组TLR2蛋白和mRNA表达较对照组显著升高， Gs-Rbl组TLR2蛋白[（0.593±0.018/0.344±0.024）比（0.975±0.022/0.564±0.031）]和mRNA [（0.349±0.015/0.401±0.021）比（0.576±0.029/0.853±0.043）]表达较阿霉素组显著下降， P均＜0.01；（2）不管是体内抑或是体外研究，阿霉素组TLR4蛋白和mRNA表达较对照组显著升高， Gs-Rbl组 TLR4蛋白[（0.371±0.013/0.254±0.027）比（0.654±0.032/0.519±0.013）]和mRNA [（1.140±0.021/0.503±0.022）比（1.602±0.013/0.838±0.021）]表达较阿霉素组显著下降， P均＜0.01。结论：阿霉素可能通过TLR2和TLR4促发慢性心力衰竭进程，人参皂甙Rbl改善阿霉素慢性心力衰竭效应与抑制T L R2和T L R4有关。%Objective:To explore whether the effect relieving chronic heart failure (CHF) induced by Adriamycin of Ginsenoside-Rbl (Gs-Rbl ) is related to inhibiting Toll-like receptor (TLR ) . Methods :Adriamycin-induced CHF model rats were randomly divided into Adriamycin group (n=15) and Gs-Rb1 group (70 mg/kg d ,n=17);another 10 normal rats were regard as control group .Neonate rat cardiomyocytes were also randomly divided into control group ,Adriamycin group (1 μmol/L) and Gs-Rb1 group (1 μmol/L Adriamycin + 200 μmol/L Gs-Rbl) .After the intervention being performed ,echocardiography and expressions of TLR2/TLR4 gene and protein were assessed in all groups .Results:(1) Both studies in vivo and in vitro indicated that expressions of TLR 2 protein and mRNA in Adriamycin group were significantly higher than those of control group ,compared with Adriamycin group ,there were significant reductions in expressions of TLR2 protein [ (0.975 ± 0.022/0.564 ± 0.031) vs .(0.593 ± 0.018/0.344 ± 0.024)] and mRNA [ (0.576 ± 0.029/0.853 ± 0.043) vs .(0.349 ± 0.015/0.401 ± 0.021)] in Gs-Rbl group ,P<0.01 both ;(2) No matter study in vivo or in vitro ,expressions of TLR4 protein and mRNA in Adriamy-cin group were significantly higher than those of control group ,compared with Adriamycin group ,there were signif-icant reductions in expressions of TRL4 protein [ (0.654 ± 0.032/0.519 ± 0.013 ) vs . (0.371 ± 0.013/0.254 ± 0.027)] and mRNA [ (1.602 ± 0.013/0.838 ± 0.021) vs .(1.140 ± 0.021/0.503 ± 0.022)] in Gs-Rbl group , P<0.01 both .Conclusion:Adriamycin may trigger the process of CHF through increasing TLR 2 and TLR4. The effect of Gs-Rbl improving adriamycin-induced CHF may be related to inhibition of TLR 2 and TLR4 .