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Effect And The Possible Underlying Mechanisms Of Hyperin On Rat Abdominal Aortic Rings And Basilar Arteries

Posted on:2011-05-27Degree:MasterType:Thesis
Country:ChinaCandidate:Q H WangFull Text:PDF
GTID:2154360305980663Subject:Pharmacology
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Hyperin (hyperin, hyperoside, Hyp), a compound of flavonol glycoside, widely exists in various kinds of plants, such as Malvaceae, Clusiaceae, Leguminosae, Ericaceae and so on; and it is also the active ingredient of many kinds of botanical medicines, e.g. yellow marshmallow, dodder, hawthorn, etc. Its chemical structure is quercetin-3-O-β-Dgalactopyranose. This laboratory has found that Hyp can inhibit calcium influx into nerve cells ,and that it also has a significant protective effect on the injury of the global cerebral ischemia- reperfusion. And there are professional reports said that Hyp can fall dog's blood pressure and inhibit the isolated rabbits'aortic contraction caused by noradrenaline, which indicates that Hyp has diastolic effect on rabbits'blood vessel. But the mechanism of Hyp's vasodilation has not been reported. Therefore, this experiment intended to observe diastolic effect on rats'blood vessel, and to explore its mechanism.Purposes:1. To evaluate the relaxation effects of Hyp on rat abdominal aortic , and to assess whether the effects of EDHF were involved in the mechanism.2. To evaluate the relaxation effects of Hyp on rat basilar arteries.3. To evaluate the effects about membrane potential of Hyp on the basilar arteries in global cerebral ischemia-reperfusion rats.Methods: 1. The isolated rat abdominal aortic rings were mounted in organ baths and changes in isometric tension were measured by using force-displacement transducer built in multi myograph system. In this model it was observed that the relaxation effects of Hyp and the possible underlying mechanisms.2. The basilar arteries in vitro were used to observe the relaxation effects to drugs. In this model it was observed that the relaxation effects of Hyp and whether it was related to the basilar arteries endothelium.3. The operation of global cerebral ischemia reperfusion injury was executed by pullsinelli 4 vessel occlusion.In this model it was observed that the hyperpolarizing action of Hyp to the basilar arteries.Results:1. The isolated rat abdominal aortic rings were mounted in organ baths and changes in isometric tension were measured by using force-displacement transducer built in multi myograph system.In 30mmol/L KCl-or1×10-7mol/L 9,11-dideoxy-11α,9α-epoxy-methanoprostaglandin F2α(U46619)-precontracted endothelium-intact rings, 1×10-6.5-1×10-4 mol/L Hyp induced concentration-dependent relaxations with maximal relaxation (Emax) of 52.2±7.2% and 80.7±4.1%, respectively. This effect was markedly reduced in endothelium-denuded rings (Emax of 15.4±1.2% in KCl-precontracted rings and 21.6±1.2% in U46619-precontracted rings).2. Hyp-induced relaxations to endothelium-intact rings were significantly attenuated after treatment with nitric oxide synthase inhibitor Nω-l-Arginine Methyl Ester (L-NAME, 3×10-4 mol/L), but not affected by indomethacin (Indo, 1×10-5 mol/L), a prostaglandin synthetase inhibitor. Relaxation induced by Hyp in U46619-precontracted endothelium-intact rings was further inhibited by combination of L-NAME and Indo (Emax of 36.6±1.9 %), and this left relaxation is more potent than Hyp-induced relaxation in endothelium-denuded rings.3. The basilar arteries in vitro were used to observe the relaxation effects to drugs. In the rat basilar arteries, preconstricted by 1×10-7mol/L U46619 in vitro, Hyp (1×10-6.5-1×10-4mol/L) had the concentration-dependent relaxations with maximal relaxation (Emax) of 66.7±1.6%, and the effects was markedly reduced in endothelium-denuded basilar arteries (Emax of 22.6±2.7% ).4. After using different concentrations of Hyp (25, 50, 100 mg/kg) and reperfusion of 60min, we measured the membrane potential of basilar artery in the global cerebral ischemia-reperfusion rats. The results show that Hyp (50, 100 mg/kg) has a significant effect on global cerebral ischemia-reperfusion rats'basilar artery smooth muscle cells.
Keywords/Search Tags:Hyperin, rat abdominal aorta, basilar arteries, vascular relaxation, endothelium-dependent hyperpolarizing factor, global cerebral ischemia reperfusion, membrane potential
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