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槲皮素在纠正血管内皮功能状态损伤中的应用(临床与实验研究)。

APPLICATION OF QUERCETIN FOR CORRECTION OF THE IMPAIRMENT OF THE FUNCTIONAL STATE OF THE ENDOTHELIUS OF VESSELS (CLINICAL AND EXPERIMENTAL STUDY).

机构信息

State Enterprise «Institute of Gerontology DF Chebotareva NAMS of Ukraine», 67 Vyshgorodska St., Kyiv, 04114, Ukraine.

State Enterprise «Institute of Pharmacology and Toxicology NAMS of Ukraine», 14 Antona Tsedika St., Kyiv, 02000, Ukraine.

出版信息

Probl Radiac Med Radiobiol. 2020 Dec;25:321-337. doi: 10.33145/2304-8336-2020-25-321-337.

Abstract

OBJECTIVE

in the experiment, to investigate the effect of Quercetin on the NO-dependent reactions of isolated vessels involving endothelium and perivascular adipose tissue (PVAT) after a single X-ray irradiation of rats at a sublethal dose. In a clinical study, to investigate the effect of long-term use of Quercetin on the functional state of themicrovascular endothelium in the elderly patients with metabolic syndrome (MS).

MATERIAL AND METHODS

Experimental studies were performed on vascular fragments obtained from adult male rats(7-8 months) of the control group, in animals exposed to a single R-irradiation at a dose of 7 Gy and animals irradiated in the same dose, which received Quercetin orally for 14 days three times a week based on 10 mg/kg bodyweight. Fragments of the thoracic aorta (TA) and mesenteric artery (MA) were cleaned of perivascular adipose tissue (PVAT-) or left uncleaned (PVAT+), and then were cut into rings (up to 2 mm). The amplitude of the contractionof the rings TA and MA under the influence of phenylephrine (PE, 3 x 10-6 M), the amplitude of the contraction of therings TA and MA in the presence of a competitive blocker of NO-synthase methyl ester of N-nitro-L-arginine(L-NAME, 10-5 M), the amplitude of relaxation of the rings TA and MA in the presence of N-acetylcysteine (NAC, 10-4 M)were measured. The clinical study examined 110 patients with MS criteria in accordance with ATP III (2001).Patients in the main group for 3 months received Quercetin from the same manufacturer, 80 mg three times a day,patients in the control group received placebo.

RESULTS

Single R-irradiation disrupts the regulation of the contractile function of TA and MA, which is evidenced bychanges in the contractile reactions of isolated fragments of these vessels as a response to the action of vasoactivecompounds. Course use of Quercetin in irradiated rats leads to the normalization of contractile and dilatory vascular responses due to partial correction of NO metabolism in the endothelium and PVAT. For the majority of patients(69 %) who received Quercetin, a post-occlusive hyperemia test showed a statistically significant increase of maximal volumetric velocity of the skin blood flow rate and duration of the recovery period to the baseline, which indicates about improvement of vasomotor vascular endothelial function.

CONCLUSIONS

Course use of Quercetin improves the functional state of the microvascular endothelium among theelderly people with MS, normalizes contractile and dilatory vascular responses in irradiated rats due to partial correction of NO metabolism in the endothelium and PVAT.

摘要

目的

在实验中,研究单次亚致死剂量 X 射线照射大鼠后,槲皮素对涉及内皮细胞和血管周脂肪组织(PVAT)的 NO 依赖的血管反应的影响。在一项临床研究中,研究长期使用槲皮素对代谢综合征(MS)老年患者微血管内皮功能的影响。

材料和方法

实验研究在成年雄性大鼠(7-8 个月)的血管片段上进行,对照组动物暴露于 7Gy 的单次照射下,实验组动物在相同剂量下照射,并每周口服 3 次 10mg/kg 体重的槲皮素,共 14 天。胸主动脉(TA)和肠系膜动脉(MA)的片段清除血管周脂肪组织(PVAT-)或保留(PVAT+),然后切成环(最大 2mm)。在苯肾上腺素(PE,3x10-6M)的作用下测量 TA 和 MA 环的收缩幅度,在竞争型一氧化氮合酶抑制剂 N-硝基-L-精氨酸甲酯(L-NAME,10-5M)存在下测量 TA 和 MA 环的收缩幅度,在 N-乙酰半胱氨酸(NAC,10-4M)存在下测量 TA 和 MA 环的松弛幅度。临床研究按照 ATP III(2001)标准检查了 110 名 MS 患者。主要组患者连续 3 个月接受同一厂家的槲皮素治疗,每日 3 次 80mg,对照组患者接受安慰剂。

结果

单次照射破坏了 TA 和 MA 收缩功能的调节,这表现在这些血管的分离片段对血管活性物质作用的收缩反应的变化。在照射大鼠中连续使用槲皮素可导致内皮细胞和 PVAT 中 NO 代谢的部分纠正,从而使血管收缩和舒张反应正常化。对于大多数接受槲皮素治疗的患者(69%),闭塞后充血试验显示皮肤血流最大容积速度和恢复至基线的恢复期的统计学显著增加,这表明血管运动性血管内皮功能有所改善。

结论

连续使用槲皮素可改善 MS 老年患者微血管内皮的功能状态,通过部分纠正内皮细胞和 PVAT 中的 NO 代谢,使照射大鼠的血管收缩和舒张反应正常化。

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