Low molecular weight fucoidan against renal ischemia-reperfusion injury via inhibition of the MAPK signaling pathway.
Low molecular weight fucoidan against renal ischemia-reperfusion injury via inhibition of the MAPK signaling pathway.
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DOI：
10.1371/journal.pone.0056224
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Chen J;Wang W;Zhang Q;Li F;Lei T;Luo D;Zhou H;Yang B
缺血再灌注损伤（IRI）是自体肾和移植肾急性肾损伤（阿基）的主要原因。本研究的目的是评估低分子量岩藻聚糖（LMWF）是否可以在动物模型和体外细胞模型中减轻肾脏IRI，并研究LMWF保护IRI的机制。雄性小鼠右肾缺血30 min再灌注24 h，或假手术切除左肾。IR后肾脏出现特征性的形态学改变，如肾小管扩张和刷状缘丢失。LMWF可明显改善IR所致的肾功能损害，降低MPO、MDA和SOD的异常水平，抑制MAPK通路的激活，从而降低线粒体细胞色素c的释放，降低Bax/Bcl-2比值和caspase-3/caspase-3比值，降低p53的磷酸化水平。LMWF可减轻缺氧-复氧或CoCl 2诱导的HK 2肾小管上皮细胞活力丧失和Δ m耗散，提示LMWF可能通过剂量依赖性降低MAPK通路活性而抑制细胞凋亡途径。我们的体内和体外研究表明，LMWF通过抑制MAPK信号通路改善急性肾脏IRI。这些数据提供的证据表明，LMWF可能作为一个潜在的治疗剂急性肾IRI。
Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) in both native and transplanted kidneys. The objective of the present study was to evaluate whether low-molecular-weight fucoidan (LMWF) could attenuate renal IRI in an animal model and in vitro cell models and study the mechanisms in which LMWF protected from IRI. Male mice were subjected to right renal ischemia for 30 min and reperfusion for 24 h, or to a sham operation with left kidney removed. Kidneys undergone IR showed characteristic morphological changes, such as tubular dilatation, and brush border loss. However, LMWF significantly corrected the renal dysfunction and the abnormal levels of MPO, MDA and SOD induced by IR. LMWF also inhibited the activation of MAPK pathways, which consequently resulted in a significant decrease in the release of cytochrome c from mitochondria, ratios of Bax/Bcl-2 and cleaved caspase-3/caspase-3, and phosphorylation of p53. LMWF alleviated hypoxia-reoxygenation or CoCl2 induced cell viability loss and ΔΨm dissipation in HK2 renal tubular epithelial cells, which indicates LMWF may result in an inhibition of the apoptosis pathway through reducing activity of MAPK pathways in a dose-dependent manner. Our in vivo and in vitro studies show that LMWF ameliorates acute renal IRI via inhibiting MAPK signaling pathways. The data provide evidence that LMWF may serve as a potential therapeutic agent for acute renal IRI.
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影响因子：
7.4
作者：
Circu, Magdalena L.;Aw, Tak Yee
通讯作者：
Aw, Tak Yee
影响因子：
5.3
作者：
Hsu, Ming-Jen;Hsu, Chung Y.;Lin, Chien-Huang
通讯作者：
Lin, Chien-Huang
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
影响因子：
4.8
作者：
Lake, Andrew C.;Vassy, Roger;Letourneur, Didier
通讯作者：
Letourneur, Didier
DOI：
10.1073/pnas.0438011100
发表时间：
2003-03-04
影响因子：
11.1
作者：
Lei, K;Davis, RJ
通讯作者：
Davis, RJ