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生物类黄酮曲克芦丁通过抑制 STAT3 信号通路预防子痫前期。

The bioflavonoid troxerutin prevents gestational hypertension in mice by inhibiting STAT3 signaling.

机构信息

Department of Obstetrics, Zibo Central Hospital, No. 54 of Gongqingtuan West Road, Zhangdian District, Zibo, 255000, Shandong Province, China.

Department of Scientific Education and Communication Cooperation, Zibo Central Hospital, No. 54 of Gongqingtuan West Road, Zhangdian District, Zibo, 255000, Shandong Province, China.

出版信息

Hypertens Res. 2021 Apr;44(4):399-406. doi: 10.1038/s41440-020-00568-z. Epub 2020 Oct 30.

DOI:10.1038/s41440-020-00568-z
PMID:33122822
Abstract

Gestational hypertension is a high-risk disease for women, and the current treatments have limited efficacies. Here, we aimed to evaluate troxerutin, which is a natural monomer of flavone, in the treatment of gestational hypertension. Pregnant mice with or without pregnancy-induced hypertension (PIH) were treated with troxerutin (20 and 40 mg/kg) or vehicle. Blood pressure and proteinuria were monitored during treatment. The expression of vasodilation converting enzyme (VCE), angiotensin, TNFα, IL-6, IL-1β and IL-10 was measured by enzyme-linked immunosorbent assay (ELISA). Oxidative stress was assessed by measuring the reactive oxygen species (ROS) levels and antioxidant enzyme concentrations. Western blot analysis was used to assess the expression of p-STAT3, STAT3, SHP-1, and RNF6. Troxerutin reduced blood pressure and the expression of VCE, angiotensin, urinary protein and pro-inflammatory cytokines in a dose-dependent manner while increasing the expression of anti-inflammatory cytokines. The levels of ROS were decreased, and the levels of antioxidant enzymes were increased. Troxerutin treatment significantly suppressed STAT3/RNF6 signaling. Overexpression of RNF6 attenuated the effects of troxerutin in ameliorating inflammation and oxidative stress. Our data support the use of troxerutin for reducing gestational hypertension due to the role of troxerutin in reducing inflammation and oxidative stress.

摘要

妊娠期高血压是一种对女性健康具有高度风险的疾病,目前的治疗方法疗效有限。在这里,我们旨在评估曲克芦丁,一种黄酮类的天然单体,在治疗妊娠期高血压中的作用。有或没有妊娠高血压(PIH)的怀孕小鼠用曲克芦丁(20 和 40mg/kg)或载体处理。在治疗过程中监测血压和蛋白尿。通过酶联免疫吸附测定(ELISA)测量血管舒张转化酶(VCE)、血管紧张素、TNFα、IL-6、IL-1β和 IL-10 的表达。通过测量活性氧(ROS)水平和抗氧化酶浓度来评估氧化应激。Western blot 分析用于评估 p-STAT3、STAT3、SHP-1 和 RNF6 的表达。曲克芦丁以剂量依赖性方式降低血压和 VCE、血管紧张素、尿蛋白和促炎细胞因子的表达,同时增加抗炎细胞因子的表达。ROS 水平降低,抗氧化酶水平升高。曲克芦丁处理显著抑制了 STAT3/RNF6 信号通路。RNF6 的过表达减弱了曲克芦丁改善炎症和氧化应激的作用。我们的数据支持使用曲克芦丁来降低妊娠期高血压,因为曲克芦丁在减轻炎症和氧化应激方面发挥了作用。

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