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ERK1/2 信号通路的激活增强子痫前期大鼠滋养细胞的增殖和凋亡。

Activation of the ERK1/2 signaling pathway enhances proliferation and apoptosis of trophoblast in preeclampsia rats.

机构信息

Department of Obstetrics, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.

出版信息

Eur Rev Med Pharmacol Sci. 2021 Jan;25(2):598-604. doi: 10.26355/eurrev_202101_24617.

DOI:10.26355/eurrev_202101_24617
PMID:33577012
Abstract

OBJECTIVE

The aim of this study was to investigate the influences of the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway on preeclampsia rats as well as the proliferation and apoptosis of trophoblasts.

MATERIALS AND METHODS

A proper number of conceived rats were applied to prepare the preeclampsia model (group P). Meanwhile, others were enrolled as control group (group C). The differences in placental structure between the two groups were compared via hematoxylin-eosin (HE) staining. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were compared between the two groups as well. In addition, T25 cell lines were divided into three groups, including Control group, hypoxia/reoxygenation (H/R) group and H/R + Staurosporine group (an activator of the ERK1/2 signaling pathway). The protein expression of phosphorylated (p)-ERK1/2 in the aforementioned model groups and cells was detected through Western blotting. Cell apoptosis rate was determined by a flow cytometer. Moreover, methyl thiazolyl tetrazolium was utilized to measure the proliferative capacity of trophoblasts in the three groups. Transwell chamber assay was adopted to count the transmembrane cells.

RESULTS

The cells in group P were arranged disorderly. Group P had remarkably lower SOD activity but higher MDA content than group C (p<0.05). The protein expression levels of ERK1/2 and p-ERK1/2 in the placenta of group C were evidently higher than those of group P (p<0.05). Besides, the protein expression levels of ERK1/2 and p-ERK1/2 were markedly up-regulated in Control group when compared with H/R + Staurosporine group, with the lowest in H/R group (p<0.05). The proliferative capacity of cells was gradually enhanced in the three groups with the increase of culture time. Cell proliferation was the strongest in Control group, followed by H/R + Staurosporine group and H/R group (p<0.05). The apoptosis and death rates of cells were the highest in H/R group, followed by H/R + Staurosporine group and Control group (p<0.05). However, the number of transmembrane cells was the largest in Control group, followed by H/R + Staurosporine group and H/R group (p<0.05).

CONCLUSIONS

The ERK1/2 signaling pathway is associated with preeclampsia in rats, whose activation can enhance cell proliferation and weaken cell apoptosis.

摘要

目的

本研究旨在探讨细胞外信号调节激酶(ERK)1/2 信号通路对先兆子痫大鼠的影响,以及对滋养细胞增殖和凋亡的影响。

材料与方法

将适量受孕大鼠用于制备先兆子痫模型(P 组),同时将其他大鼠纳入对照组(C 组)。通过苏木精-伊红(HE)染色比较两组胎盘结构的差异。比较两组超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。此外,将 T25 细胞系分为三组,包括对照组、缺氧/复氧(H/R)组和 H/R+Staurosporine 组(ERK1/2 信号通路的激活剂)。通过 Western blot 检测上述模型组和细胞中磷酸化(p)-ERK1/2 的蛋白表达。通过流式细胞仪测定细胞凋亡率。此外,采用噻唑蓝比色法测定三组滋养细胞的增殖能力。采用 Transwell 室试验计数跨膜细胞。

结果

P 组细胞排列紊乱。与 C 组相比,P 组 SOD 活性明显降低,MDA 含量明显升高(p<0.05)。C 组胎盘 ERK1/2 和 p-ERK1/2 蛋白表达水平明显高于 P 组(p<0.05)。此外,与 H/R+Staurosporine 组相比,对照组 ERK1/2 和 p-ERK1/2 蛋白表达水平明显上调,H/R 组最低(p<0.05)。随着培养时间的延长,三组细胞的增殖能力逐渐增强。对照组细胞增殖能力最强,其次是 H/R+Staurosporine 组和 H/R 组(p<0.05)。H/R 组细胞凋亡和死亡率最高,其次是 H/R+Staurosporine 组和对照组(p<0.05)。然而,对照组跨膜细胞数量最多,其次是 H/R+Staurosporine 组和 H/R 组(p<0.05)。

结论

ERK1/2 信号通路与大鼠先兆子痫有关,其激活可增强细胞增殖,减弱细胞凋亡。

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