PDF(Pubmed)
Abstract：
UNASSIGNED: 3,4-Dihydroxyl-phenyl lactic acid (DLA) and notoginsenoside R1 (R1) are known to protect ischemia and reperfusion (I/R) injury by targeting Sirtuin1/NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10/the Mitochondrial Complex I (Sirt-1/NDUFA10/Complex I) and Rho-associated kinase/adenosine triphosphate (ROCK/ATP) ATP synthase δ subunit (ATP 5D), respectively. We hypothesized that a composite of the two may exhibit a more potent effect on I/R injury. The study was designed to test this hypothesis.
UNASSIGNED: Male Sprague-Dawley rats underwent left anterior descending artery occlusion and reperfusion, with or without DLA, R1, or a combination of 3,4-dihydroxyl-phenyl lactic acid and notoginsenoside R1 (DR) pretreatment. Heart function, myocardial morphology, myocardial infarct, myocardial blood flow (MBF), apoptosis, vascular diameter, and red blood cell (RBC) velocity in venules were evaluated. Myeloperoxidase (MPO), malondialdehyde (MDA), and 8-oxo-deoxyguanosine (8-OHdG) were assessed. The content of ATP, adenosine diphosphate (ADP), and adenosine monophosphate (AMP), the activity of mitochondrial respiratory chain Complex I and its subunit NDUFA10, the Mitochondrial Complex V (Complex V) and its subunit ATP 5D, Sirt-1, Ras homolog gene family, member A (RhoA), ROCK-1, and phosphorylated myosin light chain (P-MLC) were evaluated. R1 binding to Sirt-1 was determined by surface plasmon resonance.
UNASSIGNED: DLA inhibited the expression of Sirt-1, the reduction in Complex I activity and its subunit NDUFA10 expression, the increase in MPO, MDA, and 8-OhdG, and apoptosis. R1 inhibited the increase in the expression of RhoA/ROCK-1/P-MLC, the reduction of Complex V activity and its subunit ATP 5D expression, alleviated F-actin, and myocardial fiber rupture. Both DLA and R1 reduced the myocardial infarction size, increased the velocities of RBC in venules, and improved MBF and heart function impaired by I/R. DR exhibited effects similar to what was exerted, respectively, by DLA and R1 in terms of respiratory chain complexes and related signaling and outcomes, and an even more potent effect on myocardial infarct size, RBC velocity, heart function, and MBF than DLA and R1 alone.
UNASSIGNED: A combination of 3,4-dihydroxyl-phenyl lactic acid and notoginsenoside R1 revealed a more potent effect on I/R injury via the additive effect of DLA and R1, which inhibited not only apoptosis caused by low expression of Sirt-1/NDUFA10/Complex I but also myocardial fiber fracture caused by RhoA/ROCK-1 activation and decreased expression of ATP/ATP 5D/Complex V.
UNASSIGNED: Male Sprague-Dawley rats underwent left anterior descending artery occlusion and reperfusion, with or without DLA, R1, or a combination of 3,4-dihydroxyl-phenyl lactic acid and notoginsenoside R1 (DR) pretreatment. Heart function, myocardial morphology, myocardial infarct, myocardial blood flow (MBF), apoptosis, vascular diameter, and red blood cell (RBC) velocity in venules were evaluated. Myeloperoxidase (MPO), malondialdehyde (MDA), and 8-oxo-deoxyguanosine (8-OHdG) were assessed. The content of ATP, adenosine diphosphate (ADP), and adenosine monophosphate (AMP), the activity of mitochondrial respiratory chain Complex I and its subunit NDUFA10, the Mitochondrial Complex V (Complex V) and its subunit ATP 5D, Sirt-1, Ras homolog gene family, member A (RhoA), ROCK-1, and phosphorylated myosin light chain (P-MLC) were evaluated. R1 binding to Sirt-1 was determined by surface plasmon resonance.
UNASSIGNED: DLA inhibited the expression of Sirt-1, the reduction in Complex I activity and its subunit NDUFA10 expression, the increase in MPO, MDA, and 8-OhdG, and apoptosis. R1 inhibited the increase in the expression of RhoA/ROCK-1/P-MLC, the reduction of Complex V activity and its subunit ATP 5D expression, alleviated F-actin, and myocardial fiber rupture. Both DLA and R1 reduced the myocardial infarction size, increased the velocities of RBC in venules, and improved MBF and heart function impaired by I/R. DR exhibited effects similar to what was exerted, respectively, by DLA and R1 in terms of respiratory chain complexes and related signaling and outcomes, and an even more potent effect on myocardial infarct size, RBC velocity, heart function, and MBF than DLA and R1 alone.
UNASSIGNED: A combination of 3,4-dihydroxyl-phenyl lactic acid and notoginsenoside R1 revealed a more potent effect on I/R injury via the additive effect of DLA and R1, which inhibited not only apoptosis caused by low expression of Sirt-1/NDUFA10/Complex I but also myocardial fiber fracture caused by RhoA/ROCK-1 activation and decreased expression of ATP/ATP 5D/Complex V.
摘要：
■已知3,4-二羟基苯基乳酸（DLA）和三七皂苷R1（R1）通过靶向Sirtuin1/NADH脱氢酶（泛醌）1α亚复合物10来保护缺血和再灌注（I/R）损伤/线粒体复合物I（Sirt-1/NDUFA10/复合物I）和Rho相关激酶/ATP三磷酸腺苷（ROCK亚基）分别。我们假设两者的复合物可能对I/R损伤表现出更有效的作用。这项研究旨在检验这一假设。
■雄性Sprague-Dawley大鼠接受左前降支动脉闭塞和再灌注,不管有没有DLA,R1,或3,4-二羟基苯基乳酸和三七皂苷R1(DR)的组合预处理。心功能,心肌形态学,心肌梗塞,心肌血流量（MBF），凋亡，血管直径,并评估小静脉中红细胞（RBC）的速度。髓过氧化物酶(MPO),丙二醛（MDA），和8-氧代脱氧鸟苷（8-OHdG）进行评估。ATP的含量,二磷酸腺苷（ADP），和一磷酸腺苷（AMP），线粒体呼吸链复合物I及其亚基NDUFA10，线粒体复合物V（复合物V）及其亚基ATP5D的活性，Sirt-1,Ras同源基因家族,成员A(RhoA),评价ROCK-1和磷酸化肌球蛋白轻链(P-MLC)。通过表面等离子体共振测定R1与Sirt-1的结合。
■DLA抑制了Sirt-1的表达，复合物I活性的降低及其亚基NDUFA10的表达，MPO的增加，MDA,和8-OhdG，和凋亡。R1抑制RhoA/ROCK-1/P-MLC的表达增加,复合物V活性及其亚基ATP5D表达的降低，减轻F-肌动蛋白，和心肌纤维破裂.DLA和R1都减少了心肌梗死的大小，增加了小静脉中红细胞的速度，改善MBF和I/R损害的心功能DR表现出与所施加的效果相似的效果，分别,DLA和R1在呼吸链复合物和相关信号传导和结果方面，对心肌梗塞的大小有更有效的影响，红细胞速度,心脏功能,和MBF比DLA和R1单独。
■3,4-二羟基苯基乳酸和三七皂苷R1的组合通过DLA和R1的累加作用对I/R损伤具有更有效的作用，不仅抑制了Sirt-1/NDUFA10/ComplexI的低表达引起的细胞凋亡，而且抑制了RhoA/ROCK-1活化引起的心肌纤维断裂和ATP/5D复合物的表达减少。
■雄性Sprague-Dawley大鼠接受左前降支动脉闭塞和再灌注,不管有没有DLA,R1,或3,4-二羟基苯基乳酸和三七皂苷R1(DR)的组合预处理。心功能,心肌形态学,心肌梗塞,心肌血流量（MBF），凋亡，血管直径,并评估小静脉中红细胞（RBC）的速度。髓过氧化物酶(MPO),丙二醛（MDA），和8-氧代脱氧鸟苷（8-OHdG）进行评估。ATP的含量,二磷酸腺苷（ADP），和一磷酸腺苷（AMP），线粒体呼吸链复合物I及其亚基NDUFA10，线粒体复合物V（复合物V）及其亚基ATP5D的活性，Sirt-1,Ras同源基因家族,成员A(RhoA),评价ROCK-1和磷酸化肌球蛋白轻链(P-MLC)。通过表面等离子体共振测定R1与Sirt-1的结合。
■DLA抑制了Sirt-1的表达，复合物I活性的降低及其亚基NDUFA10的表达，MPO的增加，MDA,和8-OhdG，和凋亡。R1抑制RhoA/ROCK-1/P-MLC的表达增加,复合物V活性及其亚基ATP5D表达的降低，减轻F-肌动蛋白，和心肌纤维破裂.DLA和R1都减少了心肌梗死的大小，增加了小静脉中红细胞的速度，改善MBF和I/R损害的心功能DR表现出与所施加的效果相似的效果，分别,DLA和R1在呼吸链复合物和相关信号传导和结果方面，对心肌梗塞的大小有更有效的影响，红细胞速度,心脏功能,和MBF比DLA和R1单独。
■3,4-二羟基苯基乳酸和三七皂苷R1的组合通过DLA和R1的累加作用对I/R损伤具有更有效的作用，不仅抑制了Sirt-1/NDUFA10/ComplexI的低表达引起的细胞凋亡，而且抑制了RhoA/ROCK-1活化引起的心肌纤维断裂和ATP/5D复合物的表达减少。
