Effect of GW0742 on endothelial dysfunction induced by high glucose in isolated rat thoracic aorta
10.3969/j.issn.1001-1978.2015.12.010
- VernacularTitle:GW0742对高糖损伤大鼠胸主动脉内皮的保护作用
- Author:
Lai XUE
;
Yang WU
;
Bo HUANG
;
Rong LI
;
Qingsong JIANG
- Publication Type:Journal Article
- Keywords:
GW0742;
high glucose;
endothelial dys-function;
PPAR β;
NF-κB;
eNOS;
NO
- From:
Chinese Pharmacological Bulletin
2015;(12):1675-1680,1681
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effect of GW0742 on the endothelial dysfunction induced by high glucose
(glucose at 55 mmol · L -1 )in isolated rat thoracic aorta and its related mechanisms.Methods The end
othelium-dependent relaxation of acetylcholine was per-formed in the absence or presence of GW0742 at differ-ent concentrations under high glucose condition.The structure of aorta was observed by HE staining.Moreo-ver,the content of NO was also measured by nitrate re-duction method.The mRNA and protein expression were detected by quantitative real-time PCR and West-ern blot,respectively.Results Compared with the control group,acetylcholine-induced vasodilatation was impaired by high glucose.Meanwhile,the structures of endothelial cells and smooth muscle cells were also in-terrupted.Furthermore, the expressions of PPARβmRNA and protein reduced while the NF-κB p65 ex-pression increased significantly which occurred in par-
allel with decreasing eNOS expression and NO concen-tration (P <0.01 ).GW0742 (0.01 ,0.1 ,1 μmol· L -1 )restored the relaxation of acetylcholine in a dose-dependent manner,and reversed the mRNA and pro-tein expression of PPARβ,NF-κB p65 and eNOS,as well as NO content (P <0.01 ).Conclusion GW0742 attenuates the injury of endothelial dysfunc-tion induced by high glucose,which may be,at least partly,mediated by the up-regulation of PPARβ,then the down-regulation of NF-κB,and the activation of eNOS-NO signal pathway.
