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目的确定碘对比剂碘克沙醇对小鼠肾小球入球和出球小动脉张力的影响,以及小动脉张力主要调节剂血管紧张素Ⅱ和一氧化氮(NO)的相互功能作用。材料与方法动物实验符合柏林健康和社会事务办公室伦理要求的规定。由136只C57BL/6小鼠分离得到肾小球动脉,采用常规溶液和碘沙克醇(23mgI/mL)灌注20min,随后注射血管紧张素Ⅱ。采用DAF-FM和二氢乙锭(DHE)荧光染色进行NO生物利用度和过氧化物浓度的定量测试。对所获的时间和剂量数据重复测量进行非参数检验。结果在碘沙克醇组,入球小动脉的直径从9.2μm减少到8.3μm;而对照组的血管直径则从8.7μm增大到9.3μm(P=0.008)。NO合成酶抑制剂可扩大碘沙克醇所诱导的血管收缩效应,使血管直径从9.9μm减小到5.8μm(P<0.0001)。DAF-FM荧光染色显示碘沙克醇和NO合成酶抑制剂时更低(3.6%和3.7%与对照组10.7%,P=0.009和P=0.049),提示NO的生物利用障碍。应用碘沙克醇时,DHE荧光染色的比例增高12%(P<0.0001)。血管紧张素Ⅱ的反应会被碘沙克醇或碘沙克醇灌注后NO合成酶抑制剂所增强(3.3μm和4.3μm,对照组为7.5μm,血管紧张素Ⅱ为1×10-6mol/L,两者均P=0.03)。与此不同的是,出球小动脉的直径和对血管紧张素Ⅱ的反应均没有受到碘沙克醇的显著影响。结论碘沙克醇对于入球小动脉比出球小动脉更为显著的影响可能造成对比剂所致急性肾损害时的肾小球滤过率降低。NO生物利用率的减低和过氧化物浓度的增高可解释碘沙克醇灌注之后入球小动脉的张力和反应性增高。
Objective To determine the effect of iodixanol, an iodine contrast agent, on the glomerular intima and the afferent arterioles in mice and the interaction between angiotensin Ⅱ and nitric oxide (NO), a major regulator of arteriolar tension. Materials and methods Animal experiments are in line with the ethical requirements of the Berlin Office of Health and Social Affairs. Glomerular arteries were isolated from 136 C57BL / 6 mice, perfused for 20 min with conventional solutions and ioshacrolol (23 mgI / mL) followed by angiotensin II. Quantitation of NO bioavailability and peroxide concentration using DAF-FM and ethidium (DHE) fluorescence staining. Non-parametric tests were repeated for repeated measurements of time and dose data obtained. Results In the ioxabanil group, the diameter of the arterioles decreased from 9.2 μm to 8.3 μm, while the diameter of the control group increased from 8.7 μm to 9.3 μm (P = 0.008). NO synthase inhibitors augmented the vasoconstrictive effect induced by ioxabac, reducing the vessel diameter from 9.9 μm to 5.8 μm (P <0.0001). DAF-FM fluorescence staining showed lower levels of Iodosulfan and NO synthase inhibitors (3.6% vs 3.7% vs 10.7%, P = 0.009 and P = 0.049), suggesting a bioavailability of NO. The DHE fluorescent staining increased by 12% (P <0.0001) when iodosalakol was applied. The response of angiotensin II was enhanced by NO synthase inhibitors after perfusion with ioshagrol or iodosalicylic (3.3 μm and 4.3 μm, 7.5 μm for controls and 1 × 10 -6 mol / L, both P = 0.03). In contrast, neither the diameter of the ascending arterioles nor the response to angiotensin II was significantly affected by ioxalastol. CONCLUSIONS: The more pronounced effect of iosalakol on the arterioles intima-media than in the arterioles on the arterioles may reduce the glomerular filtration rate during contrast-induced acute kidney injury. The reduction in NO bioavailability and the increase in peroxide concentration explain the increased tension and reactivity of the arteriole after injection of iosalapat.