کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4012447 1261195 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Systemic administration of HMG-CoA reductase inhibitor protects the blood–retinal barrier and ameliorates retinal inflammation in type 2 diabetes
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی و میکروب شناسی (عمومی)
پیش نمایش صفحه اول مقاله
Systemic administration of HMG-CoA reductase inhibitor protects the blood–retinal barrier and ameliorates retinal inflammation in type 2 diabetes
چکیده انگلیسی

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are frequently used lipid-lowering drugs in type 2 diabetes. Recent emerging evidence suggests that statins protect cardiovascular function via lipid-independent mechanisms. However, the potential role of statins in diabetic retinopathy in type 2 diabetes is largely unclear. In the present study we have investigated the effect of lovastatin on blood–retinal barrier and inflammatory status in the retina of db/db mice and in cultured retinal cells. Male C57BL/KsJ db/db mice were randomly chosen to receive gastric gavage of lovastatin (10 mg/kg/day) or vehicle control for 6 weeks. Retinal vascular permeability, the tight junction and inflammation were determined. The results showed that db/db mice at the age of 19 weeks exhibited significantly increased retinal vascular leakage and decreased tight junction protein level in the retina. Moreover, the expression of pro-inflammatory factors, e.g. ICAM-1 and TNF-α, was drastically up-regulated in diabetic retina. Lovastatin treatment normalized all of these changes. In cultured bovine retinal capillary endothelial cells (RCECs) and human ARPE-19 cells, lovastatin attenuated the decrease of tight junction protein (occludin) and adherens junction protein (VE-cadherin) expression-induced by TNF-α, a major pro-inflammatory cytokine in diabetic retinopathy. Lovastatin also attenuated TNF-α expression in RCEC. Towards the mechanism, we showed that lovastatin ameliorated ICAM-1 expression-induced by hypoxia and TNF-α in both RCECs and ARPE-19 cells, in part through inhibition of NF-κB activation. Taken together, these findings indicate that lovastatin protects blood–retinal barrier in diabetic retinopathy, which is likely via its anti-inflammatory effects.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Eye Research - Volume 89, Issue 1, 15 June 2009, Pages 71–78
نویسندگان
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