Resveratrol improves vascular endothelial injury induced by high-calorie and high-cholestrol diet through reduced ERS and increased eNOS expression
10.3969/j.issn.1001-1978.2014.12.028
- VernacularTitle:白藜芦醇通过减缓内质网应激及增加 eNOS 的表达改善高热量高胆固醇饮食引起的内皮损伤
- Author:
Jingjing CHENG
;
Li CHEN
;
Chaofei LI
;
Guanjun CHEN
;
Yingying BAO
;
Yunxia LU
- Publication Type:Journal Article
- Keywords:
endoplasmic reticulum stress;
endothelial damage;
resveratrol;
endothelial nitric oxide synthase;
high-calorie and high-cholestrol diet;
palmitic acid
- From:
Chinese Pharmacological Bulletin
2014;(12):1756-1762
- CountryChina
- Language:Chinese
-
Abstract:
Aim To study whether the mechanisms in-volved in resveratrol′s protective effects on vascular en-dothelial injury induced by high-calorie and high-chol-estrol diet are concerned with ERS and the change of eNOS expression. Methods Twenty-four male C57BL/6 mice were randomly divided into standard control diet (SCD),high-calorie and high-cholestrol diet(HCD)and HCD group treated with resveratrol (HCD +RES,400 mg·kg -1 ·d -1 ,1 2 weeks).Then the thoracic aorta was separated,embedded and sliced to analyze the pathological changes by HE and resor-cinol staining.The protein distribution of eNOS was measured with immunohistochemical analysis.The up-stream and downstream genes of ERS in thoracic aorta were detected by RT-PCR.After the pretreatment with different concentrations of resveratrol,the mouse aortic endothelial cells (MAECs)were treated with palmitic acid,then the changes of cell proliferation in each group were compared.Western blot,immunofluores-cence and immunohistochemistry were used to deter-mine the protein expressions of GRP78,CHOP and eNOS respectively.Results Mice fed with HCD showed thickening of thoracic aortic wall and disorgan-ized elastic fibers as compared with those in SCD group.The mRNA levels of ERS related genes were all increased obviously (P <0.05),while the protein expression of eNOS was decreased.Compared with HCDgroup,the thickened wall and the disorganized elasticfibers were improved significantly,the mRNA levels ofERS related genes were all decreased obviously (P <0.05)and the expression of eNOS protein was increased in HCD +RES group.Compared with NCgroup, the cell proliferation was significantly decreased,meanwhile GRP78 and CHOP was significantly increased (P <0.05)and the protein expression ofeNOS was decreased in PA group.The cell proliferation was increased significantly (P <0.05),the mRNA and protein expression of GRP78 and CHOP wasobviously decreased (P <0.05),meanwhile the protein expression of eNOS was increased in the mediumand large dose of RES pretreatment groups.Conclusion Resveratrol has obvious effects of improving endothelial damages induced by HCD and decreasing cellproliferateion of MAECs induced by PA, and themechanisms are possibly related with decreased ERSand increased level of eNOS protein.