人参皂甙Rbl对阿霉素所致慢性心力衰竭大鼠心肌细胞肿瘤坏死因子的影响

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）效应是否与改善肿瘤坏死因子受体（TNFR）及其配体：肿瘤坏死因子-α（TNF-α）水平有关。方法：阿霉素诱导的CHF大鼠模型被随机分为阿霉素组（n＝15，接受阿霉素1μmol／L）和Gs-Rbl组（n＝17，在阿霉素组的基础上接受Gs-Rbl 70mg・kg－1・d－1，），另正常Wistar大鼠被设为正常对照组（n＝10）同时培养的乳鼠心肌细胞亦相应地分为正常对照组、阿霉素组和Gs-Rbl组。干预完毕后，检测并比较三组心脏超声、TNFR／TNF-α蛋白和 mRNA水平。结果：1.体内：阿霉素组和 Gs-Rbl组的 TNFR-1[蛋白（0.67±0.04） kDa ，（0.51±0.04） kDa；mRNA （0.81±0.03） bp ，（0.49±0.05） bp]，TNFR-2[蛋白（0.61±0.05） kDa ，（0.47±0.03） kDa ，mRNA （0.28±0.03） bp ，（0.18±0.04） bp]]及TNF-α[蛋白TNF-α[protein （0.28±0.04） kDa ，（0.20±0.03） kDa ，mRNA （0.67±0.05） bp ， ；（0.45±0.04） bp]水平显著高于正常对照组TNFR-1[蛋白（0.13±0.02） kDa ，mRNA （0.19±0.05） bp]， TN-FR-2[蛋白（0.24±0.01） kDa ，mRNA （0.13±0.02） bp]，及TNF-α[蛋白（0.11±0.01） kDa ，mRNA （0.26±0.05） bp]（P＜0.05或＜0.01），且Gs-Rbl组的TNFR-1，TNFR-2及TNF-α蛋白和mRNA水平显著低于阿霉素组（P＜0.05或＜0.01）；体外测定的各组结果相似，也是阿霉素组和Gs-Rbl组显著高于正常对照组（P＜0.05或＜0.01），Gs-Rbl组显著低于阿霉素组（P＜0.05或＜0.01）。结论：在阿霉素促发CHF进程中，TNFR／TNF-α的表达可能起着一定作用；人参皂甙Rbl改善阿霉素CHF效应可能与调整TNFR／TNF-α有关。%Objective:To explore whether relieving effect of Ginsenosides-Rb1 (Gs-Rb1 ) on chronic heart failure (CHF) induced by adriamycin is related to improving levels of tumor necrosis factor (TNF) receptor (TNFR) and ligand TNF-αor not .Methods:Adriamycin-induced CHF model rats were randomly divided into adriamycin group (n=15 ,received adriamycin 1 μmol/L) and Gs-Rb1 group (n=17 ,received Gs-Rb1 70 mg・kg-1 ・d-1 based on adriamycin group) ,another 10 healthy Wistar rats were selected as normal control group .Meanwhile ,cultured car-diomyocytes of neonatal rats were accordingly divided into normal control group ,adriamycin group and adriamycin+Gs-Rb1 group .After intervention ,echocardiography ,levels of TNFR/TNF-αmRNA and protein were measured and compared among three groups .Results:(1) In vivo:Compared with normal control group TNFR-1 [protein (0.13 ± 0.02) kDa ,mRNA (0.19 ± 0.05) bp] , TNFR-2 [protein (0.24 ± 0.01) kDa ,mRNA (0.13 ± 0.02) bp] ,and TNF-α [protein (0.11 ± 0.01) kDa ,mRNA (0.26 ± 0.05) bp] ,the levels of TNFR-1 [protein (0.67 ± 0.04) kDa , (0.51 ± 0.04) kDa;mRNA (0.81 ± 0.03) bp , (0.49 ± 0.05) bp] , TNFR-2 [protein (0.61 ± 0.05) kDa ,(0.47 ± 0.03) kDa , mRNA (0.28 ± 0.03) bp , (0.18 ± 0.04) bp] and TNF-α [protein (0.28 ± 0.04) kDa ,(0.20 ± 0.03) kDa ,mRNA (0.67 ± 0.05) bp , (0.45 ± 0.04) bp] significantly rose (P<0.05 or <0.01) in adriamycin group and Gs-Rb1 group;and those levels of TNFR-1 ,TNFR-2 , TNF-αprotein and mRNA of Gs-Rbl group were significant reduction than those of adriamycin group ; (2) In vitro:The results were similar , those of adriamycin group and Gs-Rb1 group were also significant rise than those of normal control group ( P<0. 05 or <0. 01 ) , those of Gs-Rbl group were significant reduction than those of adriamycin group ( P< 0. 05 or <0.01) .Conclusion:TNFR/TNF-αexpression may play a certain role in the process of adriamycin-induced CHF ;im-proving effect of Gs-Rb1 on adriamycin-induced CHF may be related to regulation of TNFR/TNF-α.