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The Effect Of Recombinant Adenovirus Vector Of Rat Proteoglycan Ⅱ In Diabetic Retinopathy

Posted on:2008-02-24Degree:MasterType:Thesis
Country:ChinaCandidate:N J LiFull Text:PDF
GTID:2144360212489570Subject:Internal Medicine
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Backgroud and ObjectiveDiabetic retinopathy (DR.) is the major clinical manifestation of diabetic microvascular disease, represent major causes of mortality and morbidity in diabetic patients by leading to blindness. It is significant to study the pathogenetic mechanisms of diabetic retinopathy. Recently some researches indicate that the pathogenetic mechanisms is relative with abnormal regulation of growth and generation in cells, and growth factor plays an important role in it. And the activation of transforming growth factor β (TGF- β ) is known to be one of the major causes of diabetic retinopathy. TGF- β is an multifunctional signal proteinum, which can adjust the expression of many target gene and play an important on the cell proliferation,apoptosis, synthesis of extracellular matrixand cell differentiation. It possesses multitude biological effect and plays multiplicity role in diabetic retinopathy.Proteoglycan II(Decorin,DCN) may be involved in the regulation of fundamental biologic functions,such as matrix assenmbly, modulating fibronectin- and thrombospondin -mediated cell adhesions. It is a natural inhibitor of TGF- β .The purpose of this study was to assess the role of TGF- β in the diabetic retinopathy and the effect of inceased decorin in synthesis on the expression of TGF- β 2 in retina.Methods1 Use streptozotocin to generate the model of diabetic rats,saline as comparison. And then choose 16 of diabetic rat randomly using ad-DCN at the 8th week, ad-LacZ as comparison. All the models were divided into four groups:group A: normal comparison;group B:diabetic rat; group C:diabetic rat using ad-DCN at the 8 th week; group D:diabetic rat using ad-LacZ comparison. 2. Use RT-PCR techniques to measure mRNA expression of TGF- β 2.Results1. Diabetic rats showed obvious clinical symptoms. At any observed time point, the body weights and blood sugar of diabetic rats, ad-DCN rats and ad-LacZ rats were smaller than those of normal rats(P<0.01).2.The TGF- β 2 mRNA in the retina of diabetic rats is lower at the 8th week, then increases with the progress of diabetes. Comparing with diabetic rats, the TGF- β 2mRNA in the retina of diabetic rat using ad-DCN is lower in the progress of study than diabetic rats group and ad-LacZ rats.ConclusionThe lower expression of TGF- β 2 at the 8 th week may be relative with thedecrease number of perithelial cell, and then increase with the progress of diabetes, higher than normal comparison . These results indicates that the increasing expression of TGF- β 2 may be concerned with the development of DR.The function of ad-DCN on down-regulation of TGF- β2 in the retina of diabeticrats indicates recombinant adenovirus vector of decorin can express in vivo and may play a role in the diabetic retinopathy.
Keywords/Search Tags:diabetic retinopathy, decorin, TGF-β2, Recombinant Adenovirus
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