Resveratrol ameliorates vasculopathy in STZ-induced diabetic rats: role of AGE-RAGE signalling.
BACKGROUND
Resveratrol (RSV) has been shown to ameliorate hyperglycaemia and hyperlipidaemia in streptozotocin-induced diabetic rats. In the present study, we examined the beneficial effects of RSV on diabetes mellitus (DM)-induced vasculopathy and explored its possible mechanism.


METHODS
Male Sprague-Dawley rats were injected with streptozotocin at 65 mg/kg body weight The induction of DM was confirmed by a fasting plasma glucose level > or = 300 mg/dL and symptoms of polyphagia and polydipsia. The DM rats were treated with or without RSV at 0.75 mg/kg body weight three times a day for 4-8 weeks. Animals were sacrificed and vessel wall histology was examined by microscopy. The vascular smooth muscle cell activation was assessed by the medial thickness, collagen deposition, and the expressions receptor for advanced glycation end product, NF-kappaB, proliferation cell nuclear antigen, and the levels of Erk1/2 phosphorylation.


RESULTS
In RSV-treated DM rats, the vascular wall thickening, collagen deposition/cross-linking, and vascular permeability were all alleviated compared with that of the untreated DM rats. The vascular smooth muscle cell of the RSV-treated rats was characterized with less proliferation, lower NF-kappaB, and Erk1/2 activation, decreased proliferation cell nuclear antigen and receptor for advanced glycation end product expression. Moreover, the plasma fructosamine was significantly reduced in RSV-treated DM rats.


CONCLUSIONS
RSV alleviated DM-induced vasculopathy through attenuation of advanced glycation end product-receptor for advanced glycation end product-NF-kappaB signalling pathway.
Jing
Yu-Hong
YH
Department of Physiology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Chen
Kuan-Hsing
KH
Yang
Shu-Han
SH
Kuo
Pei-Ching
PC
Chen
Jan-Kan
JK
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D007328:Insulin; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013267:Stilbenes; D003094:Collagen; D000077185:Resveratrol