کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2567172 1128317 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Knockdown of myeloid differentiation protein-2 reduces acute lung injury following orthotopic autologous liver transplantation in a rat model
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی پزشکی ریوی و تنفسی
پیش نمایش صفحه اول مقاله
Knockdown of myeloid differentiation protein-2 reduces acute lung injury following orthotopic autologous liver transplantation in a rat model
چکیده انگلیسی

BackgroundAcute lung injury (ALI) is a serious complication that commonly occurs during orthotopic liver transplantation (OLT). Toll-like receptor 2/4 (TLR2/4) are the main membrane receptors that respond to inflammatory stimuli and mediate NF-kappa B (NF-κB) signal pathway. We previously showed that TLR2/4 expression on monocytes and serum cytokine levels were increased in patients with ALI induced by OLT. Myeloid differentiation protein-2 (MD-2) expresses the functional domains that combines TLRs and play a key regulatory role in TLRs activation. Therefore, we hypothesized that blocking MD-2 would inhibit the TLR2/4-mediated inflammatory response and lessen ALI induced by liver transplantation.MethodThirty-two Sprague Dawley (SD) rats were randomly divided into four groups. One group received a sham operation (Group S), and the other three groups underwent orthotopic autologous liver transplantation (OALT) 48 h after intratracheal administration of saline (Model group; Group M), non-targeting siRNA (negative siRNA control group; Group NC) or siRNA against MD-2 (intervention group; Group RNAi). Lung pathology, lung water content, PaO2, and expression levels of MD-2, TLR2/4, NF-κB, TNF-α, IL-1β and IL-6 were assessed 8 h after OALT.ResultsIn Groups M and NC, OALT produced marked lung pathology with decreased PaO2 levels and increased MD-2, TLR2/4 gene and protein expression levels. Furthermore, the nuclear translocation of the NF-κB P65 subunit, was increased, as were lung concentrations of TNF-α, IL-1β and IL-6. The pathology of ALI and the severity of the above biochemical changes induced by OALT were significantly reduced in the group treated with MD-2 siRNA.ConclusionMD-2 gene knock-down attenuated the increase in TLR2/4 activation and reduced ALI after OALT.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pulmonary Pharmacology & Therapeutics - Volume 26, Issue 3, June 2013, Pages 380–387
نویسندگان
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