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严重子痫前期患者血清和尿液中硫堇增强荧光。

Serum and Urine Thioflavin-T-Enhanced Fluorescence in Severe Preeclampsia.

机构信息

From the Department of Obstetrics and Gynecology (K.R.M., C.S.B., K.M.R., S.T., I.A.B.).

and Department of Pediatrics (C.S.B., I.A.B.).

出版信息

Hypertension. 2018 Jun;71(6):1185-1192. doi: 10.1161/HYPERTENSIONAHA.118.11034. Epub 2018 Apr 23.

Abstract

Common features of amyloid-like proteotoxic aggregates are the ability to bind Congo red (congophilia) and to induce fluorescence of thioflavin-T (ThT). Based on the prior discovery that women with preeclampsia exhibit urine congophilia, we proposed that amyloid-like protein aggregates present in urine also circulate in the bloodstream and this feature is linked to disease severity and clinical phenotype. ThT fluorescence was investigated in 217 paired serum and urine samples from women with severe features of preeclampsia (n=101; median [interquartile range] gestational age [GA], 32 [29-35] weeks), mild features of preeclampsia (n=22; GA, 36 [36-37] weeks), chronic hypertension (n=15; GA, 38 [37-39] weeks), healthy pregnant controls (n=57; GA, 39 [38-39] weeks), and nonpregnant controls (n=22). Serum and urine fluorescence attributable to advanced glycation end products was measured in the same samples with correction for autofluorescence. There were no GA-related changes in ThT fluorescence, although near-term serum ThT fluorescence increased compared with nonpregnant state. Compared with healthy pregnant controls, serum and urine ThT fluorescence was increased in severe features of preeclampsia (<0.001 for both) but not in mild features of preeclampsia or chronic hypertension. Except for chronic hypertension, advanced glycation end products-related fluorescence of serum or urine did not differ from controls. Urine congophilia had a stronger relationship with preeclampsia severity compared with either urine or serum ThT fluorescence. However, serum ThT fluorescence was independently associated with clinical features of hemolysis, elevated liver enzyme levels, and low platelet levels syndrome (=0.003). We demonstrate that ThT fluorescence, a marker of amyloid-like aggregates, is increased in serum of women with preeclampsia and likely because of their cytotoxicity associated with hemolysis, elevated liver enzyme levels, and low platelet levels syndrome.

摘要

淀粉样蛋白样蛋白毒性聚集体的共同特征是能够结合刚果红(刚果红亲合性)并诱导硫黄素-T(ThT)荧光。基于先前发现子痫前期妇女的尿液具有刚果红亲合性,我们提出尿液中存在的淀粉样蛋白样蛋白聚合体也在血液中循环,这一特征与疾病严重程度和临床表型相关。在 217 对来自严重子痫前期(n=101;中位[四分位数范围]孕龄[GA],32[29-35]周)、轻度子痫前期(n=22;GA,36[36-37]周)、慢性高血压(n=15;GA,38[37-39]周)、健康孕妇对照(n=57;GA,39[38-39]周)和非孕妇对照(n=22)的妇女的血清和尿液样本中检测了 ThT 荧光。在相同的样本中,用自动荧光校正测量了血清和尿液中归因于晚期糖基化终产物的荧光。虽然与非妊娠状态相比,近期血清 ThT 荧光增加,但 ThT 荧光没有与 GA 相关的变化。与健康孕妇对照组相比,严重子痫前期患者的血清和尿液 ThT 荧光均升高(两者均<0.001),但轻度子痫前期或慢性高血压患者则不然。除了慢性高血压外,血清或尿液中的晚期糖基化终产物相关荧光与对照组没有差异。尿液刚果红亲合性与子痫前期严重程度的关系强于尿液或血清 ThT 荧光。然而,血清 ThT 荧光与溶血、肝酶水平升高和血小板计数降低综合征的临床特征独立相关(=0.003)。我们证明,ThT 荧光,一种淀粉样蛋白样聚合体的标志物,在子痫前期妇女的血清中增加,这可能是由于与溶血、肝酶水平升高和血小板计数降低综合征相关的细胞毒性所致。

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