二苯乙烯苷对多柔比星致小鼠心脏损伤的保护作用研究

目的:研究中药何首乌主要有效成分二苯乙烯苷(THSG)对多柔比星(DOX)致小鼠心脏损伤的保护作用及其机制。方法:取小鼠随机分为正常对照组、模型组和THSG高、中、低剂量组(150、100、50mg·kg-1·d-1),每组20只,THSG各剂量组灌胃给予相应药物2d,第3天除正常对照组外其余各组单剂量腹腔注射DOX15mg·kg-1建立心脏损伤模型,建模同时THSG各剂量组继续灌胃给药5d,然后处死小鼠。观察各组小鼠体重、心脏指数、存活率和心肌病理形态变化,考察小鼠血清中乳酸脱氢酶(LDH)、肌酸激酶(CK)水平及心脏组织中丙二醛(MDA)、还原型谷胱甘肽(GSH)含量。结果:与正常对照组比较,模型组小鼠体重明显减轻(P<0.01),心脏指数和存活率均略减小,LDH、CK、MDA水平均明显升高(P<0.01),GSH含量明显降低(P<0.01),可见明显的心肌纤维断裂甚至消失,心肌间质水肿并伴有局灶性心内膜下出血。与模型组比较,THSG高、中、低剂量组小鼠体重、心脏指数和存活率均无明显差异,LDH、CK、MDA水平均明显降低(P<0.05或P<0.01),GSH含量明显增加(P<0.05或P<0.01),心肌组织病理形态学变化明显好转。结论:THSG对DOX致小鼠心脏损伤具有保护作用,其机制可能与抗氧化损伤有关。

Protective Effects of THSG on Heart Injury Induced by Doxorubicin in Mice

OBJECTIVE:To study the protective effects of 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside(THSG) on doxorubicin(DOX)-induced heart injury and its mechanism.METHODS:Mice were randomly divided into normal control group,model group and THSG high-dose,medium-dose and low-dose groups(150,100,50 mg·kg-1·d-1) with 20 mice in each group.THSG groups were given relevant medicine intragastrically for 2 days.On the third day,those groups were given single dose of DOX 15 mg·kg-1 intraperitoneally to induce heart injury model except normal control group.At the same time,THSG groups were given relevant medicine for 5 days continuously.At the last,all mice were sacrificed.The body weight,heart index,survival rate and myocardial morphological changes were all observed in those groups,and LDH and CK levels in serum,MDA and GSH content in heart tissue were determined.RESULTS:Compared with normal control group,the body weight and GSH content of model group decreased significantly(P<0.01),heart index and survival rate decreased slightly while LDH,CK and MDA levels increased significantly(P<0.01).Heart muscle fiber was broken obviously even disappeared,and myocardial interstitium edema was complicated with local subendocardial myocardial hemorrhage.Compared with model group,body weight,heart index and survival rate of THSG high-dose,medium-dose and low-dose groups had no significant difference,and the levels of LDH,CK and MDA decreased significantly(P<0.05 or P<0.01);the content of GSH increased significantly(P<0.05 or P<0.01),and myocardial morphology had been improved significantly.CONCLUSION:THSG can protect mice against DOX-induced heart injury by inhibiting oxidative damage.