| Objective:1. To investigate the effect of chrysin on the relaxation of isolated rat aortic rings and its mechanisms.2. To explore the effects of chrysin on endothelial dysfunction induced by acute high glucose and its possible mechanisms.Methods:1. Using in vitro aortic ring perfusion devices, the influences of chrysin on isolated aortic ring at basic condition or contraction of the aorta induced by KCl（60 m M）and PE(10-6 mol/L) were observed, and the effects of chrysin on the blood vessels reaction induced by various inhibitors were recorded. The inhibitors included L-NAME(10-4mol/L), MB(10-5 mol/L), Indo(10-5 mol/L), 4-AP(10-3 mol/L), Ba Cl2(10-4 mol/L),Gli(10-5 mol/L) and TEA(10-3 mol/L).2. The aortic rings of each group were continually incubated for 4 h in the following medium:control group: glucose 11 m M in Krebs’ solution, highglucose group: glucose 44 m M in Krebs’ solution, mannitol group: mannitol 33 m M in Krebs’ solution. Then, the effects of chrysin on endothelial dysfunction induced by high glucose were tested by comparing the vascular relaxation induced by ACh with that of SNP.Results:1. Chrysin(10-6 mol/L,3×10-6 mol/L,10-5 mol/L,3×10-5 mol/L and 10-4 mol/L) had no effect on isolated aortic ring at basic condition.2. Chrysin had stronger vasodilatation effect in intact group than that in non-intactgroup（P<0.05）. In intact group, the values of EC50 were 4.76×10-6 mol/L for KCl and6.38×10-6 mol/L for PE, respectively. In non-intact group, the values of EC50 were1.12×10-5 mol/L for KCl and 1.64×10-5 mol/L for PE.3. Treatment of the arterial rings with the e NOS inhibitor L-NAME and the s GC inhibitor MB, but not with indomethecin or endothelium denudation, obviously affected the relaxant effects of chrysin（P<0.05）.4. When the contractions were induced by KCl or PE, 4-AP(10-3 mol/L), BaCl2(10-4 mol/L), Gli(10-5 mol/L), and TEA(10-3 mol/L) weakened chrysin-induced diastolic effect significantly（P<0.05）.5. Chrysin significantly inhibited contracting effects of KCl or PE on aorta rings in Ca2+-free medium（P<0.05）. The values of IC50 were 4.84×10-5 mol/L for KCl and6.34×10-6 mol/L for PE.6. After incubating the aortic ringst with high glucose（44 m M） for 4h,there were significant differences in ACh-induced vascular relaxation between the normal glucose group and the high glucose group. The Emax was（32.12±3.92）% and the EC50 value was 1.80×10-5 mol/L of high glucose group（P<0.01 vs control group, n=6）. The endothelium-independent relaxation induced by SNP was not significantly different between the two groups.7. Chrysin(10-6 mol/L) could reverse the decline of ACh-induced vasorelaxation response induced by high glucose（44 m M）. NOS inhibitor N-nitro-L-arginine methyl ester（L-NAME） and guanylate cyclase inhibitor methylene blue（MB） could both inhibit the protective effect of chrysin.Conclusion:1. Chrysin exerts vasodilating effect on rat isolated aorta rings in a dose-dependent manner. The mechanism might be related to promoting NO release, activating K+channels and decreasing the concentration of cytoplasmic Ca2+.2. Chrysin prevents the acute high glucose-induced dysfunction of aortic rings.The mechanism might be involved in the activation of NOS and GC. |
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