Department of Respiratory and Critical Care Medicine, Haihe Clinical College of Tianjin Medical University, Tianjin, 300350, PR China; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, PR China.
Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, PR China.
Pulm Pharmacol Ther. 2020 Oct;64:101934. doi: 10.1016/j.pupt.2020.101934. Epub 2020 Aug 15.
Dihydroquercetin (DHQ) is a potent flavonoid which has been demonstrated to have multiple biological activities including anti-inflammation activity, antioxidant activity as well as anti-cancer activity etc. Recently, many studies have focused on the antioxidant activity of DHQ. However, the use of the anti-inflammation activity of DHQ in acute lung injury (ALI) has not been reported.
Cell viability was examined by CCK-8 assay. The relative expression of miR-132-3p, FOXO3 were detected by qPCR. The levels of TNF-α, IL-6 and IL-1β were detected using enzyme-linked immunosorbent assay. The amount of apoptosis cells was detected by flow cytometry. The protein levels of Bcl-2, Bax, p-p65 and p-IκBα were measured by western blot.
We found that DHQ-induced the expression of miR-132-3p in LPS-induced ALI. Overexpression of miR-132-3p resulted in the inhibition of FOXO3 expression and then suppressed FOXO3-activated NF-κB pathway, attenuating LPS-induced inflammatory response and apoptosis.
We demonstrated FOXO3 to be a target of miR-132-3p, and DHQ could induce the expression of miR-132-3p, relieving LPS-induced ALI via miR-132-3p/FOXO3/NF-κB axis, providing a promising therapeutic target for ALI.
二氢槲皮素（DHQ）是一种有效的黄酮类化合物，已被证明具有多种生物学活性，包括抗炎活性、抗氧化活性和抗癌活性等。最近，许多研究都集中在 DHQ 的抗氧化活性上。然而，DHQ 的抗炎活性在急性肺损伤（ALI）中的应用尚未报道。
通过 CCK-8 法检测细胞活力。用 qPCR 检测 miR-132-3p、FOXO3 的相对表达。用酶联免疫吸附试验检测 TNF-α、IL-6 和 IL-1β的水平。用流式细胞术检测凋亡细胞数量。用 Western blot 测定 Bcl-2、Bax、p-p65 和 p-IκBα的蛋白水平。
我们发现 DHQ 诱导 LPS 诱导的 ALI 中 miR-132-3p 的表达。miR-132-3p 的过表达导致 FOXO3 表达的抑制，从而抑制 FOXO3 激活的 NF-κB 通路，减轻 LPS 诱导的炎症反应和细胞凋亡。
我们证明 FOXO3 是 miR-132-3p 的靶基因，DHQ 可以通过诱导 miR-132-3p 的表达来缓解 LPS 诱导的 ALI，通过 miR-132-3p/FOXO3/NF-κB 轴为 ALI 提供了一个有前途的治疗靶点。
