Effects Of PPARγ Overexpression On Insulin Resistance And NF-κB Pathway In Vascular Endothelia Of Type 2 Diabetic Rats

Objective:The study is to research the effect of PPARy overexpression on insulin resistance and NF-κB pathway in vascular endothelia of type 2 diabetic rats, by constructing recombinant adenovirus infecting type 2 diabetic rats.Methods:Male SD rats were injected with low dose streptozotocin and fed with diets enriched in fat and sugar to establish the type 2 diabetic model. Then the rats were randomly divided by 4 groups, namely, normal group(NC), insulin resistance group (IR), IR with PPARy-free adenovirus group(Vehicle), IR with PPARy recombinant adenovirus group (Ad-PPARy). After 8 weeks, the following indicators were detected:① the levels of fast plasma glucose, insulin, triglyceridees and total cholesterol in serum;② the levels of NO and Ang Ⅱ in serum;③ the expression levels of PPARy and eNOS in rat thoracic aorta;④ the vascular endothelial dependent relaxant response of rat thoracic aorta; ⑤theexpression levels of IκBα, IKKα/β, pS176-IKKa/β in rat thoracic aorta;⑥the levels of TNF-α, IL-6, sICAM-1, sVCAM-1 in serum.Results:① In IR group, the levels of fast plasma glucose, insulin, triglyceride, total cholesterol and Ang Ⅱ were significantly higher than NC group, but the levels of NO were significantly lower, it suggested the model was a perfect model.② The expression levels of PPARy in rat thoracic aorta in Ad-PPARy group were significantly higher than NC group or Vehicle group, suggesting that the adenovirusly infection was successful.③ The results showed that the overexpression of PPARy significantly upregulated the expression of eNOS andsignificantly increased the levels of NO and reduced the levels of Ang Ⅱ, this suggested PPARy overexpression significantly improve insulin resistance in vascula endothelia of type 2 diabetic rats. ④ The results showed that the PPARy overexpression increased acetylcholine (Ach)-dependent vasodilation respons of aorta,this suggested the PPARy overexpr-ession significantly the vascular endothelial dependent relaxant response in type 2 diabetic rats.⑤ The results showed thatthe PPARy overexpression downregulated the expression of IKKα/β, pS176-IKKα/β and upregulated the expression of IκBα, reduced the levels of TNF-α, IL-6,sICAM-1, sVCAM-1.Conclusion:① The overexpression of PPARy can improve insulin resistance invascular endothelia of type 2 diabetic rats.② The mechanism is that PPARy repress the IKKα/β/IκBα/NF-κB pathway to reduce inflammation.