Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Department of Rehabilitation Medicine and Health Care, Hunan University of Medicine, Huaihua, Hunan Province, China.
Pharm Biol. 2022 Dec;60(1):889-898. doi: 10.1080/13880209.2022.2058558.
The risk of contrast-induced acute kidney injury (CI-AKI) is increasing and the harm is great. Quercetin is the main active component in (L.) Medik (Malvaceae) and was reported to reduce the expression of HIF-1α.
We investigate whether quercetin improves the CI-AKI through the HIF-1α/lncRNA NEAT1/HMGB1 pathway.
HK-2 cells were treated with iohexol (200 mg/mL) for 6 h to establish a CI-AKI model. Quercetin (20 μM) was administered to CI-AKI cells cultured in dishes for 24 h. Cell morphology was observed by a fluorescence microscope. MTT and TUNEL assays were used to detect cell survival rate and apoptosis. Relative mRNA levels were measured by qRT-PCR. Protein levels were detected using western blotting. IL-6 and TNF-α protein levels were tested by Elisa assay. Targeting binding sites of HIF-1α and lncRNA NEAT1 were detected by luciferase assay.
The IC value of quercetin was 163.25 μM. The expression levels of HIF-1α, lncRNA NEAT1 and HMGB1 were upregulated in the CI-AKI cell model. Quercetin diminished cell injury and apoptosis via inhibiting HIF-1α. Silencing of HIF-1α targeting lncRNA MEAT1 diminished cell injury and apoptosis. Silencing lncRNA NEAT1 has the same effect via suppressing HMGB1 expression. Collectively, quercetin diminished cell injury and apoptosis in CI-AKI cell model via the inhibition of HIF-1α on lncRNA NEAT1/HMGB1 signalling pathway.
Quercetin diminished cell injury and apoptosis in CI-AKI cell mode via the inhibition of HIF-1α on the lncRNA NEAT1/HMGB1 signalling pathway, offering a potential novel therapeutic target for CI-AKI therapy.
对比剂诱导的急性肾损伤（CI-AKI）的风险正在增加，危害也很大。槲皮素是（L.）Medik（锦葵科）的主要活性成分，据报道可降低 HIF-1α的表达。
我们研究槲皮素是否通过 HIF-1α/lncRNA NEAT1/HMGB1 通路改善 CI-AKI。
用碘海醇（200mg/ml）处理 HK-2 细胞 6h 建立 CI-AKI 模型。用槲皮素（20μM）处理培养皿中的 CI-AKI 细胞 24h。荧光显微镜观察细胞形态。MTT 和 TUNEL 测定法检测细胞存活率和凋亡。用 qRT-PCR 测定相对 mRNA 水平。用 Western blot 法检测蛋白水平。用 Elisa 法检测 IL-6 和 TNF-α 蛋白水平。用荧光素酶测定法检测 HIF-1α 和 lncRNA NEAT1 的靶向结合位点。
槲皮素的 IC 值为 163.25μM。CI-AKI 细胞模型中 HIF-1α、lncRNA NEAT1 和 HMGB1 的表达水平上调。槲皮素通过抑制 HIF-1α 减轻细胞损伤和凋亡。沉默 HIF-1α 靶向 lncRNA MEAT1 可减轻细胞损伤和凋亡。沉默 lncRNA NEAT1 通过抑制 HMGB1 表达也有相同的效果。总之，槲皮素通过抑制 HIF-1α 对 lncRNA NEAT1/HMGB1 信号通路，减轻 CI-AKI 细胞模型中的细胞损伤和凋亡。
槲皮素通过抑制 HIF-1α 对 lncRNA NEAT1/HMGB1 信号通路，减轻 CI-AKI 细胞模型中的细胞损伤和凋亡，为 CI-AKI 治疗提供了一个新的潜在治疗靶点。
