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丹参通过ERK1/2信号通路诱导羊水过少患者离体人羊膜上皮细胞水通道蛋白3表达。

Aquaporin 3 Expression Induced by Salvia Miltiorrhiza via ERK1/2 Signal Pathway in the Primary Human Amnion Epithelium Cells from Isolated Oligohydramnios.

作者信息

Shen Q, Ma X, Hua Y, Chen M, Wang Y, Zhou Q, Ye W, Zhu X

机构信息

Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, Zhejiang 325027, China.

出版信息

Curr Mol Med. 2016;16(3):312-9. doi: 10.2174/1566524016666160225154304.

Abstract

Salvia miltiorrhiza is one of the most common Chinese herbal drugs, which is effective to treat oligohydramnios. In this study, the aim was to investigate how Salvia miltiorrhiza regulate aquaporin 3 expression in the human amnion epithelial cells (hAECs) with normal amniotic fluid volume or isolated oligohydramnios, whether via extracellular signal regulated kinase1/2 (ERK1/2) signal transduction pathway or not. Primary hAECs cultures from 120 patients were incubated with Salvia miltiorrhiza or/and ERK1/2 inhibitor-- U0126. Localization of aquaporin 3 was detected by immunohistochemistry and the expression of total ERK1/2, phospho-ERK1/2 (p-ERK1/2) and aquaporin 3 was detected by Western blot. The results were: (1) In hAECs with normal amniotic fluid volume, treatment with 10 µmol/L of U0126 for 6 h resulted in the optimal inhibition of p-ERK1/2 (P<0.05). However, the expression of total ERK1/2 or aquaporin 3 did not significantly change after different concentrations or time of U0126 treatment. Salvia miltiorrhiza significantly up-regulated aquaporin 3 expression, which was not affected by U0126. (2) In hAECs with isolated oligohydramnios, treatment with 5 μmol/L of U0126 for 2 h resulted in the optimal inhibition of p-ERK1/2 and the lowest expression of aquaporin 3 (P<0.05). Moreover, Salvia miltiorrhiza significantly up-regulated aquaporin 3 expression, which was obviously blocked by U0126. These results suggest that Salvia miltiorrhiza may regulate aquaporin 3 expression in hAECs. In addition, in hAECs with isolated oligohydramnios, Salvia miltiorrhiza may regulate the expression of aquaporin 3 via the ERK1/2 signal transduction pathway, which provides a novel thread to the improved treatment for isolated oligohydramnios.

摘要

丹参是最常用的中药材之一,对治疗羊水过少有效。在本研究中,目的是探讨丹参是否通过细胞外信号调节激酶1/2(ERK1/2)信号转导途径来调节羊水正常或孤立性羊水过少的人羊膜上皮细胞(hAECs)中aquaporin 3的表达。将120例患者的原代hAECs培养物与丹参或/和ERK1/2抑制剂——U0126一起孵育。通过免疫组织化学检测aquaporin 3的定位,并通过蛋白质印迹法检测总ERK1/2、磷酸化ERK1/2(p-ERK1/2)和aquaporin 3的表达。结果如下:(1)在羊水正常的hAECs中,用10 μmol/L的U0126处理6小时导致p-ERK1/2的最佳抑制(P<0.05)。然而,在不同浓度或时间的U0126处理后,总ERK1/2或aquaporin 3的表达没有显著变化。丹参显著上调aquaporin 3的表达,这不受U0126的影响。(2)在孤立性羊水过少的hAECs中,用5 μmol/L的U0126处理2小时导致p-ERK1/2的最佳抑制和aquaporin 3的最低表达(P<0.05)。此外,丹参显著上调aquaporin 3的表达,这明显被U0126阻断。这些结果表明丹参可能调节hAECs中aquaporin 3的表达。此外,在孤立性羊水过少的hAECs中,丹参可能通过ERK1/2信号转导途径调节aquaporin 3的表达,这为改善孤立性羊水过少的治疗提供了新的思路。

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