Triptolide ameliorates fine particulate matter-induced podocytes injury via regulating NF-κB signaling pathway
Triptolide ameliorates fine particulate matter-induced podocytes injury via regulating NF-κB signaling pathway
复制标题
雷公藤甲素通过调节 NF-κB 信号通路改善细颗粒物诱导的足细胞损伤
DOI：
10.1186/s12860-020-0248-6
复制
发表时间：
2020-02-03
影响因子：
2.8
通讯作者：
Liu, Yanwei
中科院分区：
文献类型：
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作者：
Wan, Qiang;Liu, Zhongyong;Liu, Yanwei
PM2.5与膜性肾病（MN）风险增加密切相关，然而，PM2.5是否会诱导足细胞损伤（MN的潜在病理）尚未得到深入研究。雷公藤甲素是雷公藤属（tripterygium wilfordiiHook F）中的一种活性成分，在中国经常用于治疗MN，但其对pm2.5诱导的足细胞损伤的影响仍在很大程度上未知。因此，我们评估了PM2.5对足细胞的影响，并探讨雷公藤甲素是否能改善PM2.5诱导的足细胞损伤及其可能的机制。结果雷公藤甲素预处理后的足细胞经PM2.5培养，分别用CCK-8法、流式细胞术和Transwell法检测足细胞的活力、凋亡率和迁移能力。测定足细胞乳酸脱氢酶（LDH）、丙二醛（MDA）、超氧化物歧化酶（SOD）水平、足细胞骨架、nephrin、podocin、Bcl-2、Bax、核因子κ b /p65 （NF-κB/p65）、NF-κB磷酸化抑制因子（p- i -κB α）蛋白表达。我们的数据显示，PM2.5处理显著增加了足细胞中F-actin应激纤维的紊乱、细胞核结构完整性的破坏、细胞骨架的紊乱和游离，增加了足细胞凋亡率、MDA和LDH水平，显著上调了Bax、NF-κB/p65和p- i -κB α的蛋白表达，下调了nephrin、podocin和Bcl-2的蛋白表达，显著降低了SOD水平。与未处理足细胞相比，足细胞的迁移率和活力。然而，PM2.5对足细胞的这些影响被雷公藤甲素逆转。结论雷公藤甲素可通过抑制NF-κB信号通路预防pm2.5所致足细胞损伤。
BackgroundPM2.5 is associated closely with an increased risk of membranous nephropathy (MN), however, whether PM2.5 could induce podocytes injury, the underlying pathology for MN, has not be thoroughly studied. Triptolide, an active component inTripterygium wilfordiiHook F, is frequently used to treat MN in China, but its effects on PM2.5-induced podocytes injury is still largely unknown. Therefore, we evaluated the effects of PM2.5 on podocytes, and explored whether triptolide could improve PM2.5-induced podocytes injury and the possible underlying mechanisms.ResultsPodocytes were incubated with PM2.5 after being pre-treated with triptolide, viability, apoptosis rate and migratory capacity of podocytes were determined by CCK-8 assay, flow cytometry and Transwell assay, respectively. Additionally, the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD) in podocytes, the cytoskeleton of podocytes, the protein expressions of nephrin, podocin, Bcl-2, Bax, nuclear factor kappa-B/p65 (NF-κB/p65) and phospho-inhibitor of NF-κB (p-IκBα) were measured. Our data showed that PM2.5 treatment significantly increased the disorganization of F-actin stress fibers, the damaged structural integrity of nucleus, the deranged and dissociated cytoskeleton in podocytes, increased the podocytes apoptosis rate, the levels of MDA and LDH, markedly up-regulated the protein expression of Bax, NF-κB/p65 and p-IκBα, down-regulated the protein expression of nephrin, podocin and Bcl-2, and significantly decreased the level of SOD, the migration rate and the viability of podocytes, compared with those of the untreated podocytes. These effects of PM2.5 on podocytes, however, were reversed by triptolide administration.ConclusionThese results suggest that triptolide could prevent against PM2.5-induced podocytes injury via suppressing NF-κB signaling pathway.