Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding.
Dexamethasone Suppressed LPS-Induced Matrix Metalloproteinase and Its Effect on Endothelial Glycocalyx Shedding.
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DOI：
10.1155/2015/912726
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发表时间：
2015
影响因子：
4.6
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Cui N;Wang H;Long Y;Su L;Liu D
本研究旨在探讨脓毒症致血管高通透性的机制及糖皮质激素对血管内皮细胞的保护作用。雄性SD大鼠给予非致死量内毒素(EscherichiaColial055：B5，10 mg/kg，Sigma)或无热原水。治疗组同时给予地塞米松(4 mg/kg，注射前30 )或基质金属蛋白酶(MMPs)抑制剂强力霉素(4 mg/kg，注射后30 )。内毒素处理的大鼠主动脉匀浆中MMP2(p<；0.001)和MMP9(p<；0.001)的活性和蛋白水平均显著上调，并伴随着ZO-1(p<；0.001)和Syndecan-1(p=0.011)蛋白含量的降低。地塞米松和强力霉素均能显著抑制MMPs活性，抑制ZO-1和Syndecan-1的表达。地塞米松对MMPs的抑制作用明显低于多西环素，而对内毒素血症大鼠胸主动脉Syndecan-1表达的挽救作用明显高于多西环素(p=0.03)。综上所述，MMPs的激活在调节脂多糖介导的内皮细胞扰动中ZO-1和Syndecan-1蛋白水平方面起着重要作用。地塞米松和多西环素均抑制MMPs的激活，这可能有助于挽救ZO-1和Syndecan-1的表达。
The aim of this study is to determine the mechanism of sepsis-induced vascular hyperpermeability and the beneficial effect of glucocorticoid in protecting vascular endothelium. Male Sprague-Dawley rats were given either a bolus intraperitoneal injection of a nonlethal dose of LPS (Escherichia coli 055:B5, 10 mg/kg, Sigma) or vehicle (pyrogen-free water). Animals of treatment groups were also given either dexamethasone (4 mg/kg, 30 min prior to LPS injection) or the matrix metalloproteinases (MMPs) inhibitor doxycycline (4 mg/kg, 30 min after LPS injection). Both activities and protein levels of MMP-2 (p < 0.001) and MMP-9 (p < 0.001) were significantly upregulated in aortic homogenates from LPS-treated rats, associated with decreased ZO-1 (p < 0.001) and syndecan-1 (p = 0.011) protein contents. Both dexamethasone and doxycycline could significantly inhibit MMPs activity and reserve the expressions of ZO-1 and syndecan-1. The inhibition of MMPs by dexamethasone was significantly lower than that by doxycycline, while the rescue of syndecan-1 expression from LPS-induced endotoxemic rat thoracic aorta was significantly higher in the dexamethasone-treated compared to the doxycycline-treated (p = 0.03). In conclusion, activation of MMPs plays important role in regulating ZO-1 and syndecan-1 protein levels in LPS mediated endothelial perturbation. Both dexamethasone and doxycycline inhibit activation of MMPs that may contribute to the rescue of ZO-1 and syndecan-1 expression.
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影响因子：
5.2
作者：
Roomi MW;Kalinovsky T;Monterrey J;Rath M;Niedzwiecki A
通讯作者：
Niedzwiecki A
DOI：
10.1152/ajpheart.00273.2009
发表时间：
2010-01-01
影响因子：
4.8
作者：
Cena, Jonathan J.;Lalu, Manoj M.;Schulz, Richard
通讯作者：
Schulz, Richard
影响因子：
8.8
作者：
Lalu, MM;Csont, T;Schulz, R
通讯作者：
Schulz, R
影响因子：
15.1
作者：
Hollenberg, Steven M.;Guglielmi, Massimiliano;Parrillo, Joseph E.
通讯作者：
Parrillo, Joseph E.
DOI：
10.1186/cc11503
发表时间：
2013
期刊：
Critical care (London, England)
影响因子：
--
作者：
Donati A;Tibboel D;Ince C
通讯作者：
Ince C