Simvastatin improves high-fat diet-induced kidney damages by increasing expression of adiponectin and its receptors / 实用医学杂志

Objective To probe the new mechanism of simvastatin on high-fat diet-induced kidney dam-age. Methods Female SD rats were subjected to a standard control diet(SCD)or high-fat diet(HFD)for 20 weeks,then the HFD group was randomly divided into HFD group and HFD group with simvastatin treatment (HFD+ST,10mg·kg-1·d-1 )for another 8 weeks. The expression of adiponectin,adiponectin receptors R1 and R2, Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK),peroxisome proliferator-activated receptorα(PPARα),glucose regulated protein 78(GRP78)and GADD153(CHOP)in kidney were assessed respective-ly. Results Body weight and serum lipid levels in HFD group significantly increased ,expression of adiponectin and its receptors significantly down-regulated. Phosphorylation of AMPKα and PPARα expression decreased,and expression of GRP78 and CHOP up-regulated significantly. Above indexes in simvastatin treatment groups improved significantly. Conclusion Simvastatin can improve high-fat induced kidney damages ,probably by increasing expression of adiponectin and its receptors ,decreasing endoplasmic reticulum stress.

Resveratrol improves vascular endothelial injury induced by high-calorie and high-cholestrol diet through reduced ERS and increased eNOS expression / 中国药理学通报

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 expression 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 increased in HCD +RES group.Compared with NCgroup, the cell proliferation was significantly decreased,meanwhile GRP78 and CHOP was significantly increased (P <0.05)and the protein expression ofeNOS was decreased in PA group.The cell proliferation was increased significantly (P <0.05),the mRNA and protein expression of GRP78 and CHOP wasobviously decreased (P <0.05),meanwhile the protein expression of eNOS was increased in the mediumand large dose of RES pretreatment groups.Conclusion Resveratrol has obvious effects of improving endothelial 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.