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Cardiovascular disease is the number one killer of human life and health, including myocardial ischemia / reperfusion injury, hyperlipidemia, and atherosclerosis. , Reactive oxygen species (Reactive Oxygen Spices, ROS) produce too much lead to cellular oxidative stress injury is considered to be the initiating factor of the disease in many pathogenesis of doctrine. A large number of epidemiological studies have shown that myocardial ischemia / reperfusion injury, or hyperlipidemia, oxidative stress is a common pathogenesis of both diseases. As an entry point to the anti-oxidative damage screening and evaluation of cardiovascular drugs lead compounds is the subject content. This article is divided into two parts, one of six water-soluble compounds isolated from Salvia: Dan acid A and Dan acid B, rosmarinic acid, purple oxalic acid, Danshensu and protocatechualdehyde the level of in vitro molecular oxygen free radical scavenging activity screening, to find Sal A free radical scavenging activity of the strongest. Select Sal A myocardial ischemia / reperfusion injury protective effect of; Second, I synthesized seven natural product derivatives - the new structure compounds WS070035 of WS070117 WS070120 WS070121, WS070124 WS070135 and WS070143 level of in vitro molecular oxygen radical scavenging activity screening, significant free radical scavenging effect WS070117 select WS070117 this article as the target compound anti-lipid peroxidation injury research. In the first part of the experiment, using the molecular level in vitro radical scavenging activity evaluation system colorimetry, fluorescence and chemiluminescence method tested products Dan acids A five radicals and hydrogen peroxide scavenging effect. The results showed that Sal A has significant scavenging effect on DPPH radical, superoxide anion, hydroxyl radicals, peroxyl radicals, peroxide hydrogen peroxide, nitrite, the strength of activity: DPPH gt; Over oxygen free radicals gt; the hydroxyl radical gt; peroxide hydrogen gt; peroxynitrite nitrates gt; superoxide anion. On the basis of the experimental at the cellular level to further explore the to Sal A myocardial injury induced by hypoxia / re-filling protective effect. Select rat embryonic myocardial cell line H9c2 as a model material, the use of digitized hypoxia reperfusion, 1% O2 hypoxia 12 hours reperfusion for 8 hours caused by oxidative stress injury. Positive control Tempo 100 micromol / L concentration significantly improved cell viability and mitochondrial membrane potential (Mitochondrial Membrane Potential, MMP, ΔΨm), to reduce the role of intracellular reactive oxygen species levels; Sal A 0.001,0.01,0.1, 1 and 10 micromol / L concentration, cell viability was significantly improved; 0.01, 0.1 and 1 micromol / L concentration Sal A significantly inhibited the elevated levels of free radicals during ischemia / reperfusion-induced cell and mitochondrial membrane potential decreased, suggesting that Sal A antioxidant hypoxia / reperfusion-induced myocardial injury has a protective effect. In the in vitro organ level by stopping irrigation for 20 minutes - 1 hour reperfusion injury model in rat isolated heart ischemia / reperfusion injury model, concept Chadan the acid A isolated heart protective effect. The results showed that heart coronary blood flow after reperfusion, the maximum rate of decrease of the maximum rate of rise of left ventricular pressure were significantly decreased left ventricular pressure, left ventricular end-diastolic pressure was significantly increased, showed that of coronary diastolic function and left ventricular systolic and diastolic function compromised. After a single administration of different concentrations Dan phenolic by A (0.1,0.2,0.4,0.8,1.6,3.2 and 6.4μmol / L), the four indicators have been significantly improved. This experiment were confirmed at the molecular, cellular, and from the results of the three levels of body organs, Sal A play on myocardial ischemia / reperfusion injury protective effect antioxidant, the willow students of this conclusion in the laboratory rats and Beagles myocardial ischemia / reperfusion injury in vivo has been further confirmed. In the second part of the experiment, the compound of seven new structure type I synthesis in vitro molecular level of free radicals and hydrogen peroxide scavenging activity screening found compound WS070117 is strongest free radical scavenging activity. Cellular level experimental results confirmed under WS070117 100,10,1,0.1, and 0.01μmol / L concentration can significantly inhibit TNF-alpha-induced HepG2 cells increased levels of free radicals; chemiluminescence detection results suggest WS070117 NADPH oxidase (NADPH oxidase, NOX) activity may be inhibited. In the in vivo experiment, induced by high fat diet, statins can not lower blood lipids, has obvious lipid peroxidation damage of high blood lipids-ApoE-/ - mouse model, observed WS070117 independent of the outside of the lipid-lowering overall antioxidant effects in animals, compared with normal control group, high blood lipids apoE-/ - mouse model group, liver and arteries reactive oxygen species increased significantly, atherosclerotic plaque accumulation; liver and serum lipid peroxidation physical malondialdehyde (Malondialdehyde, MDA) were significantly increased, superoxide dismutase (superoxide dismutase, SOD) activity was significantly reduced. Continuous give WS070117 (5mg/kg), compared with the model group, WS070117 administration group, the liver and arteries ROS levels decreased significantly reduced atherosclerotic plaque; significantly reduce liver and serum MDA content and SOD activity significantly increased. I that WS070117 has a significant protective effect on lipid peroxidation damage. These results suggest that the level of in vitro molecular radical scavenging experiment is to find a feasible method of screening for a fat-soluble antioxidant compounds; protect the lipid oxidative damage may be the laboratory even Ze Qin, Gao Jian and Jiang Wei Zhe students found WS070117 an important mechanism for the treatment of golden hamsters and rats hyperlipidemia; the compounds WS070117 may be a potential novel compounds for the treatment of hyperlipidemia type. As an entry point to the anti-oxidative damage in experimental myocardial ischemia / reperfusion injury and lipid over two disease models of oxidative damage, water-soluble salvianolic acid A and fat-soluble WS070117 anti-ischemic and lipids regulating two cardiovascular protective effects. The experimental results again confirmed that oxidative damage is important in the pathogenesis of myocardial ischemia and hyperlipidemia disease, there may be an important drug discovery means of looking for new cardiovascular protective effects as a drug screening evaluation.
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