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目的观察多巴胺D1受体激动剂Fenoldopam介导的血管舒张反应性在胖、瘦Zucker大鼠中的差异。方法取12~14周健康雄性胖、瘦Zucker大鼠(n=12),采用鼠尾动脉无创测压法测定血压;采用离体微血管张力测定系统,观察雄性胖、瘦Zucker大鼠肠系膜三级动脉在内皮完整与去除后,Fenoldopam(1×10-8~3×10-6 mol/L)对苯肾上腺素(PHE,1×10-5 mol/L)预收缩血管的舒张作用。用多巴胺D1受体拮抗剂SCH23390(10-7 mol/L)预孵育Zucker大鼠肠系膜动脉30min,观察Fenoldopam通过多巴胺D1受体舒张血管的特异性。采用蛋白免疫印迹法测定胖、瘦Zucker大鼠肠系膜组织多巴胺D1受体表达量的差异。结果与瘦Zucker大鼠相比,胖Zucker大鼠的血压增高。在Fenoldopam 3×10-6 mol/L时,瘦Zucker大鼠肠系膜动脉的舒张效应明显强于胖Zucker大鼠[(63.43±13.79)%比(20.75±8.60)%,P<0.01]。去内皮前后,胖、瘦Zucker大鼠肠系膜动脉对Fenoldopam的舒张效应比较,差异无统计学意义(均P>0.05)。SCH23390可以拮抗Fenoldopam对胖、瘦Zucker大鼠血管的舒张效应。蛋白免疫印迹结果显示,瘦Zucker大鼠肠系膜组织多巴胺D1受体表达量高于胖Zucker大鼠[(1.26±0.04)%比(0.74±0.06)%,P<0.01]。结论与瘦Zucker大鼠相比,胖Zucker大鼠血压增高;增高的血压可能与肠系膜动脉多巴胺D1受体表达量下降引起的Fenoldopam的血管舒张效应下降有关。
Objective To observe the differences in the vasodilatory responses mediated by Fenoldopam, a dopamine D1 receptor agonist, in fat and thin Zucker rats. Methods Healthy male fat and thin Zucker rats (n = 12) were selected from 12 to 14 weeks. The blood pressure was measured by non-invasive measurement of tail artery. The isolated rat capillaries were used to observe the changes of mesenteric level Arteriosclerosis induced by phenylephrine (PHE, 1 × 10-5 mol / L) pre-contractile vasodilatation of Fenoldopam (1 × 10-8 ~ 3 × 10-6 mol / L) The Zucker rat mesenteric artery was pre-incubated with dopamine D1 receptor antagonist SCH23390 (10-7 mol / L) for 30 min to observe the specificity of Fenoldopam for vasodilation through the dopamine D1 receptor. The protein expression of dopamine D1 in mesenteric tissue of fat and thin Zucker rats was detected by Western blotting. Results Compared to lean Zucker rats, the blood pressure was increased in fat Zucker rats. At Fenoldopam 3 × 10-6 mol / L, the diastolic effect of mesenteric artery in lean Zucker rats was significantly stronger than that in fat Zucker rats [(63.43 ± 13.79)% vs (20.75 ± 8.60)%, P <0.01]. There was no significant difference in the diastolic effect of mesenteric artery between Fenugreek and Zucker rats before and after the endothelium treatment (all P> 0.05). SCH23390 antagonizes the vasodilatory effect of Fenoldopam on the blood vessels of fat and skin-bearing Zucker rats. Results of western blotting showed that the expression of dopamine D1 receptor in mesenteric tissue in lean Zucker rats was significantly higher than that in fat Zucker rats [(1.26 ± 0.04)% vs (0.74 ± 0.06)%, P <0.01]. Conclusions Compared with lean Zucker rats, the blood pressure is increased in fat Zucker rats. Elevated blood pressure may be related to the decreased vasodilation effect of Fenoldopam induced by the decrease of dopamine D1 receptor in mesenteric artery.