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红细胞生成素模拟肽(pHBSP)纠正子痫前期大鼠模型中的血管内皮功能障碍。

Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia.

机构信息

Department of Pharmacology and Clinical Pharmacology, Institute of medicine, Belgorod State National Research University, 308015 Belgorod, Russia.

Department of Obstetrics and Gynecology FPE, Kursk State Medical University, 305000 Kursk, Russia.

出版信息

Int J Mol Sci. 2020 Sep 15;21(18):6759. doi: 10.3390/ijms21186759.

Abstract

Preeclampsia is a severe disease of late pregnancy. Etiological factors and a pathogenetic pattern of events still require significant clarification, but it is now recognized that a large role is played by placentation disorders and emerging endothelial dysfunction. The administration of short-chain peptides mimicking the spatial structure of the B erythropoietin chain may become one of the directions of searching for new drugs for preeclampsia prevention and therapy. Simulation of ADMA-like preeclampsia in Wistar rats was performed by the administration of a non-selective NOS blocker L-NAME from the 14th to 20th day of pregnancy. The administration of the pHBSP at the doses of 10 µg/kg and 250 µg/kg corrected the established morphofunctional disorders. The greatest effect was observed at a dose of 250 µg/kg. There was a decrease in systolic and diastolic blood pressure by 31.2 and 32.8%, respectively ( < 0.0001), a decrease in the coefficient of endothelial dysfunction by 48.6% ( = 0.0006), placental microcirculation increased by 82.8% ( < 0.0001), the NOx concentration was increased by 42,6% ( = 0.0003), the greater omentum edema decreased by 11.7% ( = 0.0005) and proteinuria decreased by 76.1% ( < 0.0002). In addition, there was an improvement in the morphological pattern of the fetoplacental complex and the ratio of BAX to Bcl-2 expression which characterizes the apoptotic orientation of the cells.

摘要

子痫前期是一种严重的妊娠晚期疾病。病因和发病机制仍需要大量阐明,但现在认为胎盘功能障碍和新出现的内皮功能障碍起着重要作用。模拟 B 型促红细胞生成素链空间结构的短链肽可能成为寻找子痫前期预防和治疗新药的方向之一。通过在妊娠第 14 至 20 天给予非选择性 NOS 阻滞剂 L-NAME 来模拟 ADMA 样子痫前期。在 10 µg/kg 和 250 µg/kg 的剂量下给予 pHBSP 可纠正已建立的形态功能障碍。在 250 µg/kg 剂量下观察到最大效果。收缩压和舒张压分别降低 31.2%和 32.8%(<0.0001),内皮功能障碍系数降低 48.6%(=0.0006),胎盘微循环增加 82.8%(<0.0001),NOx 浓度增加 42.6%(=0.0003),大网膜水肿减少 11.7%(=0.0005),蛋白尿减少 76.1%(<0.0002)。此外,胎-胎盘复合体的形态模式得到改善,BAX 与 Bcl-2 表达的比值改善,这表明细胞凋亡的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/660b/7554893/13cf10bf88f9/ijms-21-06759-g001.jpg

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