| Objective:By observing the acute toxicity of the compound Sanqi Tongmai Tablet on mice in order to understand the toxicity and safety of the preparations; By observing blood flow effcts on the rat’s meningeal microcirculation, the effcts of in acute hypoxic state, the brain index and water content effcts in acute incomplete cerebral ischemia model in rat, explore its mechanism. Through observation of thrombosis, blood stasis model rats in vivo anti-thrombotic, anti-blood clotting, promote fibrinolysis and other indicators, and further explore the mechanism of the treatment of ischemic cerebrovascular disease in this product.By observing the signs on the nerves of MCAO rats, learning and memory function, vasoactive substances, oxygen free radicals and brain tissue morphology, etc. to explore the mechanism of the treatment for ischemic cerebrovascular disease.Methods:Give mice the compound Sanqi Tongmai piece30%suspension of0.4g/kg orally, and as the maximum tolerated dose method to observe the acute toxicity of this product; In accordance with the compound Sanqi Tongmai tablet4times2times1times of the clinical equivalent of preparation of the investigational drug. We built meningeal microcirculation model of rats, mice model in acute hypoxia; rats with acute incomplete cerebral ischemia model, thrombosis model and blood stasis model of rats, to investigate the treatment of this product for ischemic the mechanism of cerebrovascular disease by the relevant indicators.We built MACO model, to observe neurological signs in rats, learning and memory function, and vasoactive substances, oxygen free radicals, and the morphology of brain tissue to explore the mechanism of its treatment of ischemic cerebrovascular disease.Results:Acute toxicity test in mice does not appear poisoning and death, so it can not determine the LD50.The maximum tolerated dose of the compound Sanqi Tongmai films was given to mice, no significant toxic effects, the dose is about360times of the human clinical. The impact of the meningeal microcirculation in rats, in contrast with the blank control group, treatment group tended to increase microcirculatory blood flow changes with time. This product can significantly extend the breathing time of acute cerebral ischemia, increased respiratory rate, medium dose obvious; extending hypoxia tolerance, high-dose obvious. The impact for the index and water content of cerebral ischemia model in rat brain, the cerebral index of the treatment group significantly reduced compared with the control group, the water content was significantly higher. This product can be significantly prolonged electrical stimulation of the rat common carotid artery thrombosis time, extend the TT, the PT,to reduce the FIB content, and linearly related to dose. Could significantly increase the TXB2content in rat plasma enhanced PAI, Plg activity, decreased plasma6-Keto-PGF1a in content, and was linearly correlated with dose. MCAO rats with acute cerebral ischemia and recovery process, the product can significantly promote the recovery of learning and memory function, reduce the level of NO to reduce NO nerve injury, increased of SOD, decrease MDA content, reduce hippocampal CA1neurons mortality and nerve cell iNOS expression, promotion of local microvascular, accelerate the recovery of MCAO rats brain function.Conclusion:The toxicity tests confirmed the clinical safety of this product. Pharmacodynamic studies confirmed this product has to improve the microcirculation of the meninges, the protection of brain ischemia, antithrombotic, anticoagulant, anti-platelet aggregation and promote fibrinolysis, promote the role of thrombus recanalization. Have a significant protective effect on cerebral ischemia, can reduce infarct zone, protecting ischemic neurons, and improve the brain function. |
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