将代谢组学与分子生物学方法相结合,研究了丹参多酚酸盐治疗扩张性心肌病的作用机制.采用主成分分析(PCA)法,分析了健康组、模型组及丹参多酚酸盐给药组大鼠血清代谢轮廓,采用正交校正的偏最小二乘判别分析(OPLS-DA)法寻找潜在的生物标记物,共鉴定得到磷酯酰丝氨酸[16∶0/18∶1(9Z)]、溶血磷脂(16∶0)、溶血磷脂[20∶4(5Z,8Z,11Z,14Z)]、溶血磷脂[22∶6(4Z,7Z,10Z,13Z,16Z,19Z)]、胆固醇硫酸酯、胆汁酸、γ-亚麻酸、二十二碳五烯酸和9'-羧基-γ-生育酚9种潜在的生物标记物.其中,γ-亚麻酸、二十二碳五烯酸和9'-羧基-γ-生育酚的含量在模型组中下降,经丹参多酚酸盐治疗后含量上升.通过Western bloting法和酶联免疫吸附法证实丹参多酚酸盐通过影响体内与γ-亚麻酸和9'-羧基-γ-生育酚相关的超氧化物岐化酶(SOD)、丙二醛(MDA)及其下游Bcl-2和Bax蛋白分子表达量,从而减少氧化应激所致的心肌细胞凋亡数量,达到治疗阿霉素所致扩张型心肌病的目的.
Metabonomics combined with molecular biology were used to investigate the mechanisms of antidilated cardiomyopathy treated by depside salt from Salvia miltiorrhiza. The serum metabolic profiling of control group,model group and treatment group were analysed by principle component analysis( PCA). The potential biomarkers were selected with the help of orthogonal partial least squares discriminant analysis( OPLS-DA). As results,nine potential biomarkers including the PS[16 ∶ 0/18 ∶ 1( 9Z) ],Lyso PC( 16 ∶ 0),Lyso PC[20 ∶ 4( 5Z,8Z,11 Z,14Z) ],Lyso PC[22 ∶ 6( 4Z,7Z,10 Z,13Z,16 Z,19Z) ],cholesterol sulfate,taurohyocholate,γ-linolenic acid,docosapentaenoic acid and 9'-carboxy-γ-chromanol were identified respectively. In addition, the relative content of γ-linolenic acid, docosapentaenoic acid and 9'-carboxy-γ-chromanol decreased in the model group,while increased in the treatment group. With the help of western bloting and enzyme-linked immunosorbent method,we confirmed that the depside salt from Salvia miltiorrhiza influenced the expression levels of superoxide disproportionation( SOD),malondialdehyde( MDA),Bcl-2 and Bax protein molecule( the proteins mentioned above were related with γ-linolenic acid and 9'-carboxyl-γ-tocopherol),and then reduced the amount of the apoptosis myocardial cell induced by oxidative stress,and treated the the dilated cardiomyopathy caused by adriamycin finally.