Shen Q, Ma X, Hua Y, Chen M, Wang Y, Zhou Q, Ye W, Zhu X
Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, Zhejiang 325027, China.
Curr Mol Med. 2016;16(3):312-9. doi: 10.2174/1566524016666160225154304.
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.
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。